MX2008014689A

MX2008014689A - Pyridopyrimidinone derivatives.

Info

Publication number: MX2008014689A
Application number: MX2008014689A
Authority: MX
Inventors: Stephan Roever; Holger Kuehne; Jens-Uwe Peters; Uwe Grether; Fabienne Ricklin; Robert Narquizian; Henrietta Dehmlow; Nicole A Kratochwil; Constantinos Panousis; Aurelia Conte
Original assignee: Hoffmann La Roche
Priority date: 2006-05-23
Filing date: 2007-05-11
Publication date: 2008-11-27
Also published as: KR20090008390A; AU2007253513B2; EP2029601B1; WO2007134986A1; CN101448836A; AR061058A1; KR101083490B1; DE602007006947D1; JP2009537588A; BRPI0711879A2; CL2007001452A1; CA2651573C; TW200804369A; CN101448836B; US20070275987A1; IL195013A0; JP5112423B2; AU2007253513A1; ES2344086T3; EP2029601A1

Abstract

The invention is concerned with novel pyridopyrimidinone derivatives of formula (I), wherein R1 to R8, X, Y, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds are HM74A agonists and can be used as medicaments.

Description

PYRIDOPYRIMIDININONE DERIVATIVES DESCRIPTION OF THE INVENTION This invention relates to dopyrimidinone derivatives of the formula (I) ) wherein X is a single bond, O, N (R9) C (0), N (R9) C (0) 0, OC (0) NR9, N (R9) C (O) NR10 or N (R9) S02 , or, if m is 1, 2 or 3, X can also be C (0) NR9; And it is a simple link, or, if n is 1, 2, 3, 4, 5 or 6, Y can also be O; R1, R2 and R3 independently of each other are hydrogen, halogen, lower alkyl, fluorine-lower alkyl, lower alkoxy, fluorine-lower alkoxy or cycloalkyl; R5, R6 and R7 independently of each other are hydrogen, fluorine, lower alkyl or fluorine-lower alkyl, or R4 and R5 together with the carbon atom to which they are attached form a ring and -R -R5- is - (CH2) 2-6 ~ ro R6 No. Ref. : 197561 and R7 together with the carbon atom to which they are attached form a ring and -R6-R7- is - (CH2) 2_6-; R8 is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine-lower alkoxy, cycloalkyl, fluorine-cycloalkyl, cycloalkyl-oxy, C (0) OH, lower alkoxy-C (0), NH2C (0), N (H, lower alkyl) C (0), N (lower alkyl) 2C (0), OH, lower alkyl- C (O) O, NH2, (H, lower alkyl), N (lower alkyl) 2, lower alkyl-C (0) NH, lower alkyl-C (0) N (lower alkyl), NH2S02, N (H, lower alkyl) S02, N (lower alkyl) 2S02, lower alkyl-S02-NH, lower alkyl-S02-N (lower alkyl), cyano and phenyl, which is optionally substituted 1 to 3 times by substituents selected from the group formed by halogen, lower alkyl, lower alkoxy and fluorine-lower alkyl; R and R independently of each other are hydrogen, lower alkyl or fluorine-lower alkyl; m is 0, 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6; where m + n is > 1; and the pharmaceutically acceptable salts and esters thereof. The invention also relates to a process for obtaining the above compounds, to pharmaceutical compositions containing such compounds as well as to the use of these compounds for the manufacture of pharmaceutical compositions. Coronary heart disease (CHD) continues to be the leading cause of death in Western countries. In the United States, 13.2 million people, or 4.85% of the population, are affected, with 1.2 million new or recurrent attacks and 500,000 deaths every year (American Heart Association, 2001 statistics). Several well-known risk factors influence this disease, such as age, sex, blood lipids, blood pressure, smoking, diabetes, and body mass index (BMI) 'as an indicator of overweight and obesity. obesity. The Adult Treatment Panel III of the National Cholesterol Education Program (NCEP) defines high plasma levels of low density lipoprotein (LDL) cholesterol (LDL-C> 160 mg / dl) and low levels of lipoprotein high density (HDL) cholesterol (HDL-C <40 mg / dL) as independent risk factors for CHD. Many epidemiological prospecting studies indicate that a reduced level of HDL-C is an independent and significant risk factor for heart disease, whereas the increased levels of HDL-C > 60 mg / dl (> 1.55 mmol) play a protective role against CHD. Nicotinic acid has been used for almost 40 years (niacin), a vitamin B complex, as a lipid reducing drug, endowed with a favorable profile for all classes of lipoproteins. Numerous clinical studies have shown the beneficial effects of niacin, showing that it produces a reduction in coronary artery disease and mortality in general. Niacin is the most potent agent currently available to increase the HDL level. It has been proposed that the main mode of action of niacin is the inhibition of lipolysis in adipose tissue, which results in the reduction of free fatty acids (FFA) in plasma and liver and, therefore, the lower production of very low density lipoproteins (VLDL), which means a reduction in total cholesterol (TC) , triglycerides (TG) and LDL-C. Due to the lower levels of lipoproteins rich in TG, there is less modification of the HDL particles by the action of cholesteryl ester transfer protein (CETP), which results in less HDL catabolism. Direct inhibition of the absorption of lipoprotein AI-HCL (LPAI-HDL) particles in the liver has also been proposed, which could be attributed to the properties of niacin that increase total HDL (Jin et al., Arterioscler. Vasc. Biol. 7, 2020-2028, 1997). Niacin also has antidiabetic, antithrombotic and anti-inflammatory properties, which contribute to the overall cardioprotective effects. Thanks to a wide variety of mechanisms, niacin reduces thrombosis, such as the reduction of lipoprotein (a) (Lp (a)) which is a potent inhibitor of fibrinolytic activity and is the only currently authorized drug that effectively reduces serum Lp (a) levels (Carlson et al., J. Intern. Med. 226, 271-6, 1989). Inflammation is a critical component of atherosclerosis, which leads to the recruitment of macrophages, which promote plaque development and decrease plaque stability, thereby increasing cardiovascular risk. It has been suggested that niacin has anti-inflammatory properties, for example by reducing the levels of C-reactive protein (CRP) (Grundy et al., Arch. Intern. Med. 162, 1568-76, 2002). Several prospective studies have established strong and direct correlation between cardiovascular risk and CRP levels, an index of vascular inflammation. The use of niacin is not widespread because it has side effects, especially intense skin redness. HM74A / HM74, a receptor associated with protein G (GPCR), has been identified as a receptor for niacin and has been proposed as a mediator of the effects of niacin (Wise et al., J. Biol. Chem. 278 ( 11) 9869-9874, 2003, and Soga et al., Biochem. Biophys., Res. Commun. 303 (1), 364-369, 2003). As confirmation, the suppression of PUMA-G (HM74A ortholog) in mice suppresses the effects of niacin on reducing free fatty acids and triglycerides in plasma (Tunaru et al., Nature Medicine (3), 352-255, 2003 ). The new compounds of the present invention outperform the compounds already known in the art, by virtue of the fact that they bind to and activate HM74A. The compounds of the present invention are selective for HM74A, which indicates that they have a greater affinity with HM74A than with HM74. It is expected that the compounds of the present invention have a greater therapeutic potential and have fewer side effects than nicotinic acid. The compounds of the present invention can be used as medicaments for the treatment and / or prevention of diseases that are modulated with HM74A agonists. Examples of such diseases are elevated levels of lipids and cholesterol, in particular dyslipidemia, low HDL cholesterol, atherosclerosis, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, particularly diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, sepsis, inflammatory diseases (eg asthma, arthritis, colitis, pancreatitis, cholestasis / fibrosis of the liver and diseases that have an inflammatory component, eg Alzheimer's disease or disturbed / unlikely cognitive function). Unless indicated otherwise, the following definitions are established to illustrate and describe the meanings and scope of the various terms used in this invention. In this description, the term "lower" is used to indicate a group containing from one to seven carbon atoms, preferably from one to four. The term "halogen" denotes fluorine, chlorine, bromine or iodine, with fluorine, chlorine and bromine being preferred. The term "alkyl", alone or in combination with other groups, means a straight or branched chain monovalent saturated aliphatic hydrocarbon radical having one to twenty carbon atoms, preferably one to sixteen carbon atoms, with higher preference of one to ten carbon atoms. The lower alkyl groups described below are the preferred alkyl groups. The term "lower alkyl", alone or in combination with other groups, denotes a monovalent straight or branched chain alkyl moiety, having from one to seven carbon atoms, preferably from one to four. This term is illustrated with moieties of the methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl type and the like. The term "fluorine-lower alkyl" denotes alkyl moieties which are mono- or poly-substituted by fluorine. Examples of fluoro-lower alkyl groups are CFH2, CF2H, CF3, CF3CH2, CF3 (CH2) 2, (CF3) 2CH and CF2H-CF2. The term "alkenyl", alone or in combination with other groups, means a straight or branched chain hydrocarbon radical having an olefinic bond and up to 20 carbon atoms, preferably up to 16. The term "lower alkenyl" denotes a hydrocarbon radical straight or branched chain having an olefinic bond and up to 7 carbon atoms, preferably up to 4, eg 2-propenyl. The term "alkynyl", alone or in combination with other groups, denotes a straight or branched chain hydrocarbon radical having a triple bond and up to 20 carbon atoms, preferably up to 16. The term "lower alkynyl" denotes a hydrocarbon radical straight or branched chain having a triple bond and up to 7 carbon atoms, preferably up to 4, eg 2-propynyl. The term "amino", alone or in combination, means a primary, secondary or tertiary amino group, linked through the nitrogen atom, the secondary amino group bears an alkyl or cycloalkyl substituent and the tertiary amino group bears two alkyl or cycloalkyl substituents , similar or different, or the two nitrogen substituents together form a ring, for example, -NH2, methylamino, ethylamino, dimethylamino, diethylamino, methyl-ethylamino, pyrrolidin-1-yl or piperidino etc., preferably primary amino, dimethylamino and diethylamino and in particular dimethylamino. The term "cycloalkyl" denotes a monovalent carbocyclic moiety of 3 to 10 carbon atoms, preferably 3 to 7 carbon atoms, especially preferably 3 to 6 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The term "fluoro-cycloalkyl" denotes a cycloalkyl moiety that is mono- or poly-substituted by fluorine, preferably 1 to 4 times by fluorine. Examples of fluoro-cycloalkyl are 2-fluorocyclopropyl, 2,2-difluorocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 3-fluorocyclobutyl, 3,3-difluorocyclobutyl or 3, 3-difluorocyclopentyl. The term "alkoxy" denotes a group R'-O-, wherein R 'is an alkyl. The term "lower alkoxy" denotes a group R'-O-, wherein R 'is a lower alkyl. The term "fluorine-lower alkoxy" denotes a radical R "-0-, wherein R" is fluorine-lower alkyl. Examples of fluoro-lower alkoxy groups are CFH2-0, CF2H-0, CF3-0, CF3CH2-0, CF3 (CH2) 2-0, (CF3) 2CH-0 and CF2H-CF2-0. The term "aryl", alone or in combination, denotes a phenyl or naphthyl group, preferably a phenyl group, which may be optionally substituted 1 to 5 times, preferably 1 to 3 times, by substituents independently chosen from the group. group consisting of halogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy, fluoro-lower alkoxy, carboxy, carboxy-lower alkyl, lower alkoxy-carbonyl, lower alkoxy-carbonyl-lower alkyl, H2NC (0), (H, lower alkyl) C (O), (lower alkyl) 2NC (O), H2NC (O) -lower alkyl, (H, lower alkyl) NC (O) -lower alkyl, (alkyl) lower) 2NC (O) -lower alkyl, lower alkyl fluoride, H2N-lower alkyl, (H, lower alkyl) N-lower alkyl, (lower alkyl) 2N-lower alkyl, lower alkyl-S02, lower alkyl-S020, lower alkyl-S02-NH, lower alkyl-S02-N (lower alkyl), H2NS02, (H, lower alkyl) NS02, (lower alkyl) 2NS02, cyano, cycloalkyl, lower alkoxy-lower alkyl, lower alkenyl, lower alkynyl, fluorine-lower alkoxy-lower alkyl, cyano-lower alkyl, optionally substituted phenyl and optionally substituted heteroaryl. Other possible substituents are, for example, hydroxy, amino, N02, dioxo-lower alkylene (forming, for example, a benzodioxyl group), lower alkyl-carbonyl, lower alkyl-carbonyloxy, lower alkyl-carbonyl-NH, cycloalkyl, phenyl and phenyloxy. Preferred substituents are halogen, lower alkyl, cycloalkyl and optionally substituted phenyl. The aryl groups may also be substituted in the manner indicated in the description and claims that follow. The term "heteroaryl" denotes a 5- or 6-membered monocyclic aromatic ring, or a 9 to 10-membered bicyclic ring, which may have 1, 2 or 3 atoms chosen from nitrogen, oxygen and sulfur, for example furyl, pyridinyl , pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, imidazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, 1, 2, 3-thiadiazolyl, benzoimidazolyl, indolyl, indazolyl, benzisothiazolyl, benzoxazolyl, benzoisoxazolyl and quinolinyl . Preferred heteroaryl groups are pyridinyl, oxazolyl and triazolyl, especially pyridinyl. A heteroaryl group may optionally have a substitution pattern similar to that described above on the occasion of the term "aryl". In addition, the heteroaryl groups may be substituted in the manner indicated in the description and claims that follow. The term "pharmaceutically acceptable esters" embraces derivatives of the compounds of the formula (I), in which a carboxy group has been converted to an ester. The esters of lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, mono- or dialkyl lower-amino-lower alkyl, morpholino-lower alkyl, pyrrolidino-lower alkyl, piperidino-lower alkyl, piperazino- lower alkyl, lower alkyl-piperazino-lower alkyl and aralkyl are examples of suitable esters. Preferred are methyl, ethyl, propyl, butyl and benzyl esters. Methyl and ethyl esters are especially preferred. The term "pharmaceutically acceptable esters" further encompasses the compounds of the formula (I), wherein the hydroxy groups have been converted into the corresponding esters by reaction with inorganic or organic acids, for example nitric acid, sulfuric acid, phosphoric acid , citric acid, formic acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and the like, which are not toxic to living organisms. The compounds of the formula (I) can form pharmaceutically acceptable acid addition salts. Examples of the pharmaceutically acceptable salts are the salts of the compounds of the formula (I) with physiologically compatible inorganic acids, for example hydrochloric acid, sulfuric acid, sulfuric acid or phosphoric acid.; or with organic acids, for example methanesulfonic acid, p-toluenesulfonic acid, acetic acid, lactic acid, trifluoroacetic acid, citric acid, fumaric acid, maleic acid, tartaric acid, succinic acid or salicylic acid. The term "pharmaceutically acceptable salts" denotes salts of this type. In addition, the compounds of the formula (I) can form salts with bases. Examples of the salts are the alkali metal, alkaline earth metal and ammonium salts, for example the Na, K, Ca and trimethylammonium salts. The term "pharmaceutically acceptable salts" also indicates salts of this type. The salts obtained by the addition of an acid are preferred. In detail, the present invention relates to compounds of the formula (I) (I) where X is a single bond, 0, N (R9) C (0), N (R9) C (0) 0, 0C (0) NR9, N (R9) C (0) NR10 or N ( R9) S02, or, if m is 1, 2 or 3, X can also be C (0) NR9; And it is a simple link, or, if n is 1, 2, 3, 4, 5 or 6, Y can also be 0; R1, R2 and R3 independently of each other are hydrogen, halogen, lower alkyl, fluorine-lower alkyl, lower alkoxy, fluorine-lower alkoxy or cycloalkyl; R4, R5, R6 and R7 independently of each other are hydrogen, fluorine, lower alkyl or fluorine-lower alkyl, or R4 and R5 together with the carbon atom to which they are attached form a ring and -R-R5- is - ( CH2) 2-6- or R6 and R7 together with the carbon atom to which they are attached form a ring and -R6-R7- is - (CH2) 2_6-; is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine-lower alkoxy, cycloalkyl, fluorine-cycloalkyl, cycloalkyl -oxi, C (0) OH, lower alkoxy-C (0), NH2C (0), N (H, lower alkyl) C (0), N (lower alkyl) 2C (0), OH, lower alkyl-C (0) 0, NH2, N (H, lower alkyl), N (lower alkyl) 2, lower alkyl-C (0) H, lower alkyl-C (0) (lower alkyl), NH2S02, N (H, alkyl lower) S02, N (lower alkyl) 2S02, lower alkyl-S02-NH, lower alkyl-S02-N (lower alkyl), cyano and phenyl which is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen , lower alkyl, lower alkoxy and fluorine-lower alkyl; R10 independently of each other are hydrogen, lower alkyl or fluoro-lower alkyl; m is O, 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6; where m + n is > 1; and the pharmaceutically acceptable salts and esters thereof. The compounds of the formula (I) are preferred (I) where X is a single bond, 0, N (R9) C (0), N (R9) C (0) 0, 0C (0) NR9 or N (R9) C (0) NR10, or, if m is 1, 2 or 3, X can also be C (0) NR9; And it is a simple link, or, if n is 1, 3, 4, 5 or 6, Y can also be 0; R1, R2 and R3 independently of each other are hydrogen, halogen, lower alkyl, fluorine-lower alkyl, lower alkoxy, fluorine-lower alkoxy or cycloalkyl; R4, R5, R6 and R7 independently of each other are hydrogen, fluorine, lower alkyl or fluorine-lower alkyl, or R4 and R5 together with the carbon atom to which they are attached form a ring and -R4-R5- is - ( CH2) 2_6-, or R6 and R7 together with the carbon atom to which they are attached form a ring and -R6-R7- is - (CH2) 2-6- R8 is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine-lower alkoxy, cycloalkyl, fluorine-cycloalkyl, cycloalkyl-oxy, C (0) OH, lower alkoxy- C (O), NH2C (0), N (H, lower alkyl) C (O), N (lower alkyl) 2C (O), OH, lower alkyl-C (O) O, NH2, N (H, alkyl lower), N (lower alkyl) 2, lower alkyl-C (O) NH, lower alkyl-C (0) N (lower alkyl), NH2S02, N (H, lower alkyl) S02, N (lower alkyl) 2S02, lower alkyl-S02-NH, lower alkyl-S02- N (lower alkyl) rior), cyano and phenyl which is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy and fluoro-lower alkyl; R9 and R10 independently of each other are hydrogen, lower alkyl or fluorine-lower alkyl; m is 0, 1, 2 or 3; n is 0, 1, 2, 3, 4, 5 or 6; where m + n is > 1; and the pharmaceutically acceptable salts and esters thereof. The compounds of the formula (I) are individually preferred and the physiologically acceptable salts thereof are individually preferred and the pharmaceutically acceptable esters thereof are preferred individually, with the compounds of the formula (I) being especially preferred. The compounds of the formula (I) can have one or more asymmetric C atoms and therefore can exist in the form of a mixture of enantiomers, a mixture of diastereoisomers or in the form of optically pure compounds. Preferred compounds of formula (I) are those, wherein X is a single bond, O, N (R9) C (0), N (R9) C (0) 0, OC (0) NR9 or N ( R9) C (O) NR10, or, if m is 1, 2 or 3, X can also be C (0) NR9; And it is a simple link, or, if n is 1, 3, 4, 5 or 6, Y can also be O; in which R9 and R10 have the meanings defined above. Preferably, X is a single bond, O, N (R9) C (0), N (R9) C (0) 0, 0C (0) NR9 or N (R9) C (0) NR10, or, if is 1, 2 or 3, X may also be C (0) NR9, where R9 and R10 have the meanings defined above. And it is preferably a single bond, or, if n is 1, 3, 4, 5 or 6, Y can also be 0. Preferred compounds of formula (I) described above are those in which X is a single bond , 0, N (R9) C (0), N (R9) C (0) 0 or N (R9) C (0) NR10, and R9 and R10 have the meanings defined above. X is preferably a single bond, 0, N (R9) C (0) or N (R9) C (0) 0, and R9 has the meaning defined above. It is further preferred that X is N (R9) SC > 2, in which R9 has the meaning defined above. And it is more preferably a simple link. Also with greater preference, Y is 0. Each of the groups indicated for X and Y constitute individually a preferred embodiment. The X groups mentioned above are linked to the group (CR4R5) m on its left side and to the group (CR6R7) n on its right side. Another preferred embodiment of the present invention relates to compounds of the formula (I), wherein R1, R2 and R3 independently of each other are hydrogen, halogen, lower alkyl or cycloalkyl, preferably hydrogen, halogen or lower alkyl. R1 is preferably hydrogen, methyl or fluorine, more preferably hydrogen or methyl. R 2 is preferably hydrogen, methyl, ethyl, butyl, fluorine, chlorine or bromine, more preferably hydrogen, methyl or bromine. R3 is preferably hydrogen. Other preferred compounds of the present invention are those, wherein R 4, R 5, R 6 and R 7 independently of each other are hydrogen or lower alkyl. Preferably, R4, R5, R6 and R7 are hydrogen. In cases, where m or n is greater than 1, there may be more than one R4, R5, R6 or R7. In this case, the individual R4, R5, R6 or R7 may be the same or different. For example, if m is 3 and R 4 and R 5 are hydrogen or lower alkyl, the group - (CR 4 R 5) 3 can be eg -CH (CH 3) -CH 2 -CH 2 -. In addition, in cases where m or n is greater than 1, it is preferred that only one of R4 and R5 or R6 and R7 together form a cycloalkyl. In another preferred embodiment of the present invention, R8 is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine lower alkoxy or phenyl, which is optionally substituted by halogen. R8 is preferably aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy or fluorine-lower alkyl. R8 is preferably phenyl or naphthyl, the phenyl is optionally substituted by 1 or 2 substituents independently chosen from the group consisting of halogen and lower alkoxy. R8 is more preferably phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 2-methoxy-phenyl, 2-chloro-phenyl, 2-fluoro-phenyl, 3,4-dichloro-phenyl, naphthalene-1-yl. or naphthalene-2-yl. Other preferred compounds are those, wherein R8 is 3-chloro-4-fluoro-phenyl, 2,5-difluoro-phenyl or 5-methyl-2-phenyl-oxazol-4-yl. It is preferred that m is 0 or 1. It is further preferred that n is 0, 1, 2, 3 or 4. Each of the individual values indicated above for m and n respectively, individually constitute preferred embodiments of the present invention, also in combination with any of the other preferred modalities. The compounds wherein R9 and R10 are hydrogen are also preferred. In particular, the preferred compounds are the compounds of the formula (I) described in the examples as individual compounds, as well as their pharmaceutically acceptable salts and pharmaceutically acceptable esters thereof. Preferred substituents are those indicated in the specific examples that follow. Preferred compounds of the formula (I) are those selected from the group consisting of: 2-benzyloxymethyl-3H-pyrido [2], 3-d] pyrimidin-4-one, 2-phenoxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-chloro-phenoxymethyl) -3H-pyrido [2, 3-d] ] pyrimidin-4-one, 2- (5-phenyl-pentyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-methoxy-phenoxymethyl) -3H-pyrido [2, 3 -d] pyrimidin -one, 2- (4-eti1-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-phenyl-butyl) -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (4-fluoro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2-phenethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [2- (3-methoxy-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [4- (4-chloro-phenyl) -butyl] - 3H-pyrido [2,3-d] pyrimidin-4-one, 2- (6-phenyl-hexyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [4- (4- fluorine-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2-p-Tolyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2,3-dimethyl-1-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalene-1-yloxymethyl) -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- (4-chloro-2-methyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 6-methyl-2- (4-phenyl-butyl) -3H-pyrido [ 2, 3-d] pyrimidin-4-one, (4 - ??? - 3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, N- (4-oxo) -3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionam ida, N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -4-phenyl-butyramide, 6-bromo-2- (4-phenyl-butyl) - 3H-pyrido [2,3-d] pyrimidin-4-one, 6-bromo-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [3- (4-methoxy-phenyl) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-phenyl-propoxy) -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (4-phenyl-butoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [4- (4-methoxy-phenyl) -butoxy] ] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (3-pyridin-3-yl-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-phenoxy-ethoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (naphthalen-2-yloxy) -ethoxy] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2-phenethyloxymethyl-3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (3,4-difluoro-phenoxy) -propoxy ] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [3- (4-methoxy-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2 - [4- (4-Fluoro-phenyl) -3-methyl-butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [5- (4-chloro-phenyl) -pentyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [3- (4-fluoro-phenoxy) -propyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-p-tolyl-ethoxymethyl) -3H-pyrido [2,3- d] pyrimidin-4-one 2- [2- (4-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-benzyloxy-ethyl) -3H - pyrido [2,3-d] pyrimidin-4-one, 2- (4'-fluoro-biphenyl-4-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4 -m-tolyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (1-methyl-4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidine- 4-one, 2- (naphthalen-2-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, l-benzyl-3- (4-oxo-3,4-dihydro-pyrido [2 , 3-d] pyrimidin-2-ylmethyl) -urea, 2- [2- (-fluoro-phenyl) -ethoxymethyl] -6-methyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-iodo-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [ 3- (-fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidiiv 4-one, 2- (3-p-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one 2- [3- (2-fluoro-phenoxy) -propoxy] -3H-pyrido [2, 3-d] pyrimidirr-4-one, 2- (3-o-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one 2- [2- (2-Fluoro-phenyl) -ethoxymethyl] -7-methyl-3H-pyrido [2,3-d] pyrimidin-4-one, (4-oxo-3,4-dihydro-pyrido [2 , 3-d] pyrimidin-2-ylmethyl) -carbamic acid 2-chloro-benzyl, 2- [3- (3-fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one 2- (3-m-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one 2- [2- (2-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (2-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-o-tolyl) -ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one 2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2-phenethyloxy-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3,4-dichloro-benzyloxy) -3H-pyrido [2, 3 -d] pyrimidin-4-one, 2- [2- (4-fluoro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2, 4-difluoro- benzyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4-chloro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one , 2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (6-phenyl-hexyloxy) -3H-pyrido [2,3-d] pyrimidin-4 -one, 2- [3- (4-chloro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (2-chloro-phenoxy) -propoxy] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one and ( 6-methyl-4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, and the pharmaceutically acceptable salts and esters thereof. The especially preferred compounds of the formula (I) are those selected from the group consisting of: 2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalen-1-yloxymethyl) -3H-pyrido [2,3-d] pyrimidine-4 -one, 6-methyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one, (4-oxo-3,4-dihydro-pyrido [2,3-] d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, N- (4-OXO-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide, 2- [ 2- (Naphthalen-2-yloxy) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidine -4-one, 2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalen-2-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-fluoro-phenyl) -ethoxymethyl] -7-methyl-3 H -pyrido [2,3-d] pyrimidin-4-one, 2 - (3, 4-dichloro-benzyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (2-chloro-phenoxy) -propoxy ] -3H-pyrido [2, 3-d] pyrimidin-4-one and 2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, and the pharmaceutically acceptable salts and esters thereof.

Other preferred compounds, already defined above, are those selected from the group consisting of 6-chloro-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidine- 4-one, 6-chloro-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [2- ( 4-Fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [ 2, 3-d] pyrimidin-4-one, 6-chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4- ona, 6-chloro-2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 3- (3-fluoro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-fluoro-3H- pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (5-methyl-2-phenyl-oxazol-4-yl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide, 2- [1, 2, 4] Triazol-l-ylmethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-chloro-phenoxy) -N- (4-oxo-3, -dihydro-pyrido [ 2,3-] pyrimidin-2-ylmethyl) -acetamide, N- (4-OXO-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -2- (pyridin-2-yloxy) -acetamide, 2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4 -one, 7-fluoro-2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, N- (β-fluoro-4-oxo- 3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide, 7-fluoro-2- [2- (3-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 5-methyl-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- ( 3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 7-methyl-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidine-4 -one, 2- [3- (2-chloro-phenoxy) -pr opoxy] -5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3 -d] pyrimidin-4-one, 7-fluoro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 3- (2- chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 3- (3-chloro-phenyl) -N- (4- oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 2- [2- (2-chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2 , 3-d] pyrimidin-4-one, 6-chloro-2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-fluorine -2- [2- (3-Fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [4- (4-fluoro-phenyl) - butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-chloro-6-fluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2, 3 -d] pyrimidin-4-one, 2- (2-m-tolyl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4-chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin -one, 3- (4-chloro-phenyl) -N- (4- oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, (6-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidine- 2-ylmethyl) -benzylcarbamate, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, N- ( 4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-m-tolyl-propionamide, 7-fluoro-2- [2- (3-trifluoromethoxy-phenyl) - ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 3- (3-methoxy-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2 - [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, (6-chloro-4-oxo-3, 4- dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -benzylcarbamate, (7-chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamate of b encyl, (7-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -benzylcarbamate, 6-chloro-2- (2-naphthalen-2-yl) -ethoxymethyl) -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2 - [2- (3-chloro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 6-butyl-2- [2- (3-chloro-phenyl ) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-butyl-2- [2- (2,5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3 -d] pyrimidin-4-one, 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 6 -cyclopropyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one, (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidine) 2- (2-Fluoro-phenyl) -ethanesulfonic acid 2-yl-ethyl) -amide and (4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide of 2 - (3-chloro-phenyl) -ethanesulfonic acid and the pharmaceutically acceptable salts and esters thereof. Other especially preferred compounds, defined above, are those selected from the group consisting of 6-chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3- chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (5-methyl-2-phenyl-oxazol-4-yl) -N- (4 -oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide, 6-chloro-2- (3-phenoxy-propoxy) -3H-pyrido [2, 3-d] pyrimidin-4-one, (6-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -benzylcarbamate, 2- [2- (2, 5- difluoro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl- 3H-pyrido [2,3-d] pyrimidin-4-one, 6-butyl-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidine- 2- (2-Fluoro-phenyl) -etanesulf 4-one and (4-oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -amide nico and pharmaceutically acceptable salts and asters thereof. It will be appreciated that the compounds of the general formula (I) of this invention can be derivatized in their functional groups to obtain derivatives that are capable of converting again "live" into the original compound. The invention also relates to a process for obtaining the compounds of the formula (I) defined above, the process consists of converting a compound of the formula (ll) by intramolecular condensation in the compound of the formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, m, n, X and Y have the meanings defined in any of the claims 1-19 The conversion of the compound of the formula (II) into the compound of the formula (I) by an intramolecular condensation can be carried out conveniently by methods known to those skilled in the art, eg with 2-alkaloylamino -nicotinamides (V), for example under basic conditions using bases of the sodium, potassium or cesium carbonate type or sodium or potassium hydroxide, in solvents of the ethanol, methanol, water or mixtures thereof type, at elevated temperatures or at reflux, obtaining the compounds of the formula (I). Alternatively, a cyclization in an acid medium in the presence of p-toluenesulfonic acid, in a solvent of the toluene type, at elevated temperatures or under reflux. The present invention also relates to compounds of the formula (I) defined above, when they are obtained by a process as indicated above. The compounds of the formula (I), which are the subject of this invention, can be obtained in the manner indicated in reaction schemes A-C, by methods indicated in the examples or by similar methods. Unless otherwise indicated, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X, Y, m and n have the meanings defined above. The starting materials are commercial products, are compounds described in the technical literature or can be obtained by methods well known in the art. In some cases, the syntheses require carboxylic acids as starting materials, which can be obtained according to the methods described in the E-H reaction schemes.

Reaction scheme A The 3H-pyrido [2,3-d] pyrimidin-4-ones (la) with an alkyl side chain (for the case of being m = 1-3 or for m = 0 and X = a single bond) can be obtained by various methods. A method is described in the reaction scheme A. The starting materials, the 2-amino-3-cyano-pyridines (II) or the 2-amino-nicotinic acids (III) are commercial products or compounds described in the technical literature. or that can be obtained by methods well known to those skilled in the art. The 2-amino-nicotinamides (IV) can be obtained from the 2-amino-nicotinonitriles (II) by a hydrolysis step, for example with a hydroxide ion source, for example sodium or potassium hydroxide, and a catalyst, such as H2O2, in a suitable solvent, for example water, methanol or ethanol, at elevated temperatures (step a). Alternatively, the 2-amino nicotinamides (IV) can be obtained from the corresponding 2-amino-nicotinic acids (III) by conversion to the corresponding acid chlorides with thionyl chloride or oxalyl chloride in solvents of the toluene type or CH2C12, preferably at reflux and subsequent treatment of the acid chlorides with NH4OH, in solvents of the THF type (step b). The 2-amino nicotinamides (IV) can then be reacted with a suitably active carboxylic acid, for example with a chloride, bromide or carboxylic acid anhydride, in a suitable solvent, for example THF, DMF or CH2C12, optionally in the presence of a base, for example pyridine, DMAP, Huenig base, triethylamine, Na2CC > 3 or ammonium hydroxide, obtaining the 2-alkaloylamino-nicotinamides (V) which can be isolated after conventional separation, which includes a purification step, for example column chromatography (step c). Activated carboxylic acids are commercial products or compounds described in the technical literature or can be obtained by methods well known to those skilled in the art (eg RC0C1: 1. RC02H, CH2C12, (C1C0) 2, DMF, t. amb., or 2. RC02H, thionyl chloride, reflux, where R = (CR4R5) mX (CR6R7) nYR8). In a final step d can be performed intramolecular condensation with 2-alkaloylamino-nicotinamides (V), for example under basic conditions using bases of the sodium, potassium or cesium carbonate type or sodium or potassium hydroxide in solvents of the ethanol, methanol, water or mixtures thereof type, at elevated temperatures or at reflux, obtaining the 3H-pyrido [2] , 3-d] pyrimidin-4-ones (la) (step d). Alternatively, cyclization can be carried out in an acid medium in the presence of p-toluenesulfonic acid in a solvent of the toluene type, at elevated temperatures or under reflux (step e). The 3H-pyrido [2,3-d] pyrimidin-4-ones (Ib) with an ether-type side chain (m? 0 and X = O) can be obtained by reaction of the 2-amino-nicotinamides (IV) with a carboxylic acid ester (VI) (R is, for example, Me, Et, Bn or another suitable protective group, described, for example, in "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) in the presence of a base, for example by treatment of a methyl ester (VI) (R = Me) with LiHMDS (lithium hexamethyldisilazide) in THF at room temperature (step f). The asters (VI) are commercial products, compounds described in the technical literature or obtainable by methods described in reaction schemes E) -H) (eg by esterifications of carboxylic acids (III) of reaction scheme E) or carboxylic acids (V) of reaction scheme F) by methods known in the art, compounds (IV) of reaction scheme G) or compounds (III) of reaction scheme H)) or by methods that the experts in the technique they know well. The protected amines (VIII) (m F 0, R 9 is a residue already described above, except H or a protective group) can be obtained from 2-amino-nicotinamides (IV) and carboxylic acid esters (VII) very similar to that described for the compounds (Ib) (step g). Alternatively, the acid chlorides CIC (O) (CR jmKUR9) PG can be reacted with the 2-amino-nicotinamides (IV) in the manner described in steps c) -e) to obtain the compounds (VIII). Removal of the amine protecting group (s) gives the amines (IX) (R9 has a previously defined meaning) (step h). Methods for the protection and deprotection of amines are well known to those skilled in the art and have been described in the technical literature, eg in "Protective Groups in Organic Chemistry" of T.W. Greene and P.G.M. Wutts, 2nd ed., 1991, iley N.Y. For example, the phthalyl glycyl chloride is reacted with a 2-amino-nicotinamide (IV) in the presence of a pyridine-type base in a solvent of the dichloromethane type, preferably at temperatures between 0 ° C and room temperature and then it is treated at elevated temperatures in a solvent of the DMF type in the presence of a base of the ethyl-diisopropyl-amine type to obtain cyclization products (VIII) with R9 and PG forming, together, a phthalimide. The elimination of the phthaloyl protecting group can be effected, for example, by treatment with hydrazine in a solvent of the ethanol type, preferably at elevated temperatures, forming a primary amine (IX) (R9 = H). The esters (VII) and the corresponding C1C (O) acid chlorides (CR4R (R9) PG) are commercial products or compounds described in the technical literature or obtainable by methods well known to those skilled in the art. ) can be condensed with appropriately activated carboxylic acids (X) to obtain the final products (Ic) (m? 0) (step i) Activated carboxylic acids are commercial products or compounds described in the technical literature or can be obtained by methods well known to those skilled in the art (eg, carboxylic acid chlorides: 1. carboxylic acid, CH2C12, (C1C0) 2, DMF, t.amb.; or 2. carboxylic acid, thionyl chloride, reflux). Alternatively, the carboxylic acids (X) can be activated "in situ" and converted to the final products (Ic) using, for example, N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride, TBTU (0- (benzotriazol-1-yl) -N, N, N ',?' -tetramethyluronium tetrafluoroborate) or BOP (benzotriazole-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate) in the presence of a base, for example ethyl-diisopropylamine, triethylamine, N-methylmorpholine, optionally in the presence of 4-dimethylamino-pyridine or HOBt (1-hydroxybenzoate) triazole) in solvents of the dichloromethane, DMF, DMA or dioxane type at temperatures between 0 ° C and room temperature. By condensation of the amines (IX) with sulfonic acid chlorides (XI) the final products (Id) (m? 0) are obtained (step j). The formation of sulfonamides can be carried out according to methods described in the technical literature, for example reaction of the amine (IX) with a sulphonic acid chloride (XI) in the presence of a base of the ethyl-diisopropyl-amine type, a solvent of the dichloromethane type, preferably at temperatures between 0 ° C and room temperature. Sulphonic acid chlorides are commercial products or compounds described in the technical literature or obtainable by methods well known to those skilled in the art. Alternatively, the amines (IX) can be reacted with isocyanides to obtain the final products (I), in which X = NHC (0) NH, in the manner described in step g of reaction scheme B or with chloroformates to form the final products (I), in which X = NHC (0) 0 in the manner described in step h of reaction scheme B. If one of the starting materials, the compounds of the formula (IV), the activated carboxylic acid used to obtain the compounds (V), the esters (VI), the esters (VII), the carboxylic acids (X) or the sulphonic acid chlorides (XI) contain one or more functional groups which are not stable or are reactive under the conditions of one or Further reaction steps, then appropriate protective groups (PG) (as described in eg "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) may be introduced before performing the critical step, for this methods well known in the art will be used. These protective groups can be eliminated at a later stage of the synthesis by applying standard methods of the chemical literature. If the compounds (IV), the esters (VI), the esters (VII), the carboxylic acids (X), the sulphonic acid chlorides (XI) and / or the activated carboxylic acids used to obtain the compounds (V) contain chiral centers, the pyridopyrimidinones (la), (Ib), (Ic) or (Id) may be obtained in the form of mixtures of enantiomeric di-ester isomers, which may be separated by methods well known in the art, e.g. ex. HPLC (chiral) or crystallization. The racemic compounds can be separated, eg. in their antipodes by diastereomeric salts by crystallization with optically pure acids or by separation of the antipodes by specific chromatographic methods, using chiral adsorbents or chiral eluents.

Reaction scheme B Id Another method to obtain 2-alkyl-3H-pyrido [2,3-d] pyrimidin-4-ones (I) (for the case of m = 1-3 or for m = 0 and X = a single bond ) using 2-amino nicotinonitriles (II) as starting materials is described in reaction scheme B: the 2-amino nicotinonitriles (II) are reacted with an appropriately activated carboxylic acid, for example with a chloride, a bromide or a carboxylic acid anhydride, in a suitable solvent, for example THF, DF or CH2C12, optionally in the presence of a base for example pyridine, DMAP, Huenig's base, triethylamine, Na2C03 or ammonium hydroxide, obtaining 2-amino- N-acylated 3-cyano-pyridines (III) after the usual separation and purification (step a). In some cases, 2-amino-3-cyano-pyridines (IV) N, -diacylated can also be isolated. The 2-alkyl-3H-pyrido [2,3-d] pyrimidin-4-ones (I) can be obtained from compounds III by hydrolysis of the nitrile functional group and subsequent intramolecular condensation (step b). This reaction can be carried out by treating compounds III with a hydroxide ion source, for example sodium or potassium hydroxide or potassium carbonate, and a catalyst, for example H202, in a suitable solvent, for example water, methanol or ethanol, at elevated temperatures. The N, N-diacylated 2-amino-3-cyano-pyridines (IV) can be converted to monoacylated pyridines (III), for example by using an aqueous solution of calcium carbonate in the manner described in the technical literature (see, for example, B) Abarca et al., Tetrahedron 4_5, 7041-7048, 1989) (step c). Alternatively, the 2-alkyl-3H-pyrido [2,3-d] pyrimidin-4-ones (I) can be obtained from the N, N-diacylated 2-amino-3-cyano-pyridines (IV) in a series of reactions performed within a single reactor, by a selective monohydrolysis and subsequent hydrolysis of the nitrile functional group and then an intramolecular cyclization using sodium or potassium hydroxide or potassium carbonate, and a catalyst, for example H202, in a suitable solvent, example water, methanol or ethanol, at elevated temperatures (step d). In those cases in which the 3H-pyrido [2,3-d] pyrimidin-4-ones (V) or (VI) are isolated after the cyclization, the compounds can continue to be modified, optionally employing one or more protecting groups , which can be eliminated at a suitable later stage of the synthesis (steps ek). Subsequent modifications of the derivatives (V) involve the deprotection of the amine moiety, obtaining the 2-aminoalkyl-3H-pyrido [2,3-d] pyrimidin-4-ones (VII). The protecting group is removed under reaction conditions which will depend on the nature of the protecting group (step e). For example, a benzyl carbamate can be removed under acidic conditions, for example by treatment with HBr / AcOH, the amines (VII) being obtained in the form of salts, which can serve as blocks or modules for subsequent modifications. In the case of using the BOC as a protective group, the elimination may be carried out with TFA in CH2CI2. The compounds VII can be transformed with an appropriately activated carboxylic acid, for example an activated carboxylic acid "in itself" with an activating agent, for example EDCI, optionally in the presence of HOBt and a base, for example the base of Huenig, NEt3, NMM, in CH2C12, DMF, DMA or dioxane, to obtain the 3H-pyrido [2,3-d] pyrimidin-4-ones (la), which may be recovered from the reaction mixture by a conventional separation (step f) . Likewise, 3H-pyrido [2,3-d] pyrimidin-4-ones (Ib) can be obtained by reacting the compounds VII with an isocyanide in solvents of the pyridine, dichloromethane type, between room temperature and the reflux temperature ( step g) after carrying out the conventional separation and purification operations. 3 H -pyrido [2,3-d] pyrimidin-4-ones (Ic) can be obtained from compounds VII (step h) by treatment with a chloroformate and a base, for example triethylamine, NMM, or the base of Huenig, in a solvent of the dichloromethane type, carrying out the separation and purification operations. Alternatively, the amines (VII) can be condensed with chlorides of sulfonic acids C1S02 (CR6R7) nYR8 to obtain the 3H-pyrido [2,3-d] pyrimidin-4-ones (I), where X = N (R9) ) S02 as described in step j of reaction scheme A. Sulphonic acid chlorides C1S02 (CR6R7) nYRs are commercial products or compounds described in the technical literature or obtainable by methods well known to those skilled in the art. The formation of sulfonamides can be carried out according to methods already described in the technical literature, for example by reacting an amine (VII) with a sulphonic acid chloride C1S02 (CR6R7) nYR8 in the presence of a base of the ethyl-diisopropyl type -amine, in a solvent of the dichloromethane type, preferably at temperatures between 0 ° C and room temperature. If the substituent of position 2 is appropriately functionalized with a terminal acetylene motif, as in the derivatives (VI), then a Sonogashira reaction can be carried out according to the procedures already described in the technical literature with halogenated aromatic reagents, for example iodoarenes, bromoarenes or chloroarenes or with aromatic triflates (step i). The Sonogashira reaction conditions may involve the presence of a palladium catalyst and a copper catalyst, for example Pd (PPh3) 4 / CuI or Pd (OAc) 2 / CuI or PdCl2 (PPh3) 2 / CuI, and a base, for example an amine, for example triethylamine or piperidine, which can also act as a solvent, alternatively a solvent, for example THF, can be used. After the conventional separation and purification an acetylenic compound (VIII) is obtained. This can continue to be transformed (step k), with a reduction of the acetylene bond in hydrogen atmosphere with a catalyst, for example palladium on carbon, in a solvent of the ethanol type, obtaining the 3H-pyrido [2,3-d] pyrimidine 4-onas (Id). If one of the starting materials, the compounds of the formula (II) or substituents introduced in steps g, h, foi, contain one or more functional groups that are not stable or reactive under the reaction conditions, then they may be introducing protective groups (PG) (as described in eg "Protective Groups in Organic Chemistry" by TW Greene and PGM utts, 2nd ed., 1991, Wiley NY) before the critical step, applying well-known methods of the art . These protective groups can be eliminated at a later stage of the synthesis, applying standard methods described in the technical literature. If the compounds (III) or (IV) and / or the substituents introduced in steps g, h, foi contain chiral centers, the pyridopyrimidinones (I), (a), (Ib), (Ic) or (Id) may obtained in the form of mixtures of diastereomers or enantiomers, which may be separated by methods well known in the art, eg HPLC (chiral) HPLC or crystallization. The racemic compounds can be separated eg into their antipodes via the diastereomeric salts by crystallization with optically pure acids or by separation of their antipodes by applying specific chromatographic methods using a chiral adsorbent or a chiral eluent. Reaction scheme C The 3H-pyrido [2,3-d] pyrimidin-4-ones (I) (for the case of being m = 1-3 om = 0 and X = a single bond) can be synthesized from the 2-fluoro- nicotinic (II) or 2-chloro-nicotinic acid (II) in the manner described in reaction scheme C: the carboxylic acids (II) can be condensed, after appropriate activation, with amidines (III) or the corresponding salts of amidine, obtaining acylamidines (IV) under reaction conditions, which are well known to the experts (step a). If the activated carboxylic acid is for example a chloride, a bromide or a carboxylic acid anhydride, the reaction may be carried out in a solvent of the dichloromethane type, optionally in the presence of a base, for example triethylamine, ethyl-diisopropylamine or N- ethylmorpholine, at temperatures between 0 ° C and room temperature. Activated carboxylic acids are commercial products or compounds described in the technical literature or obtainable by methods well known to those skilled in the art (eg, carboxylic acid chlorides: 1. carboxylic acid, CH2C12, (C1C0) 2, DMF, t.amb .; or 2. carboxylic acid, thionyl chloride, reflux). As an alternative, the carboxylic acids (II) can be activated n "and transformed into acylamidines (IV) using, for example, N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride, TBTU (O- (benzotriazol-1-yl) -N, N, N ',' -tetramethyluronium tetrafluoroborate) or BOP (benzotriazol-l-yloxytris (dimethylamino) phosphonium hexafluorophosphate), in the presence of a base, for example ethyl -diisopropyl-amine, triethylamine, N-methylmorpholine, optionally in the presence of 4-dimethylamino-pyridine or HOBt (1-hydroxybenzo-triazole), in solvents of the dichloromethane, DMF, DMA or dioxane type, preferably at temperatures between 0 ° C and ambient temperature Amidines (III) or their corresponding salts are commercial products, compounds already described in the technical literature or compounds that can be synthesized by methods well known to those skilled in the art, For example, compounds (III) can be synthesized treating the corresponding this one of carboxylic acids (e.g. compounds (IV) of reaction scheme G) or compounds (III) of reaction scheme H) or esters which can be synthesized by esterification of the carboxylic acids (III) of reaction scheme E) or the carboxylic acids (V) of the scheme of reaction F by methods well known in the art) with trimethylaluminum chloride and ammonium in a solvent of the toluene type, preferably at temperatures between 0 ° C and room temperature. Cyclization of acylamidines (IV) in 3H-pyrido [2,3-d] pyrimidin-4-ones (I) can be carried out, for example, by treatment with a base of the type potassium tert-butylate or potassium carbonate, in a solvent of type DIVISO or DMF, at temperatures between 0 ° C and the reflux temperature of the solvent (step b). In cases where 2-fluoro-nicotinic acids (II) (R = F) are used as starting materials, activated carboxylic acids and amidines (III) directly provide the final products (I) without previously isolating the acyl-amidines (IV) (step c). These reactions are preferably carried out by treating the chlorides of acid substituted by fluorine in position 2 and the amidines (III) in the presence of a base of the type N, -diisopropyl-ethyl-amine in a solvent of the acetonitrile type, at temperatures between room temperature and the reflux temperature of the solvent. If one of the starting materials, the compounds of the formula (II) or (III), contain one or more functional groups that are not stable or are reactive under the reaction conditions, then protective groups (PG) (of the mode described eg in "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, iley NY) before the critical step, applying methods well known in the art. These protective groups can be eliminated at a later stage of the synthesis, applying standard methods described in the technical literature. Optionally, the 3H-pyrido [2,3-d] pyrimidin-4-ones carrying a protecting group can continue to be transformed after the cyclization (steps boc) to obtain the final products, as described in reaction schemes A and B. If the compounds (II) or (III) contain chiral centers, the pyridopyrimidinones (I) may be obtained in the form of mixtures of diastereomers or enantiomers, which may be separated by methods well known in the art, e.g. HPLC (chiral) HPLC or crystallization. The racemic compounds can be separated eg into their antipodes via the diastereomeric salts by crystallization with optically pure acids or by separation of their antipodes by applying specific chromatographic methods using a chiral adsorbent or a chiral eluent.

The 2-xy-3H-pyrido [2,3-d] pyrimidin-4-ones I (for the case of m = 0, X = O) can be obtained in the manner shown in reaction scheme D: the chlorides of the 2-chloronicotinic acid (II) can be obtained from the corresponding 2-chloronicotinic acids, which are commercial products, known compounds or which the experts can obtain. The reaction of the acid chlorides (II) with 2-methyl isothiourea in a solvent of the chloroform type and in the presence of a base of the pyridine type, at a temperature between 0 ° C and the reflux temperature of the solvent makes it possible to obtain the acyl -seudotioureas (III) (step a). Cyclization of the compounds (III) in a solvent, for example DMF, in a temperature range between room temperature and the reflux temperature of the solvent makes it possible to obtain the pyrimidine derivatives (IV) (step b). Treatment of the compounds (IV) with an aqueous acid, for example with hydrochloric acid, preferably at elevated temperatures, leads to the formation of the 2,4-dioxo-pyrimidines (V) (step c). Alternatively, the compounds (V) can be obtained from substituted 2-amino-nicotinic acids (IX) and urea in the manner described in the technical literature (see, for example, C. Sanmartín et al., Bioorg. Med. Chem. 1_3, 2031-2044, 2005, step g). Substituted 2-amino-nicotinic acids (IX) are commercial products or compounds already known from the technical literature or which the experts can obtain. The conversion of the 2,4-dioxo-pyrimidines (V) into the corresponding 2,4-dichloro-pyrimidines (VI) can be carried out, for example, by treatment with phosphorus oxychloride, preferably at reflux (step d). The selective displacement of the chlorine atom from position 4 of the compounds (VI), for example with aqueous sodium hydroxide at room temperature, leads to the 2-chloro-4-oxy-pyrimidines (VII) (step e). The compounds (VII) can be reacted with alcohols (VIII), obtaining the final compounds (I) (step f). This reaction can be carried out in the presence of a suitable, non-nucleophilic base, for example KOtBu, in solvents of the DMSO type, at temperatures between room temperature and the reflux temperature of the solvent, optionally employing a microwave oven. The 2-xy-3H-pyrido [2,3-d] pyrimidin-4-ones (I) can be isolated from the reaction mixture, for example by HPLC. If one of the starting materials, the compounds of the formula (II) or (IX) or the alcohols (XIII) contain one or more functional groups that are not stable or are reactive under the reaction conditions, then protective groups may be introduced (PG) (in the manner described, eg, in "Protective Groups in Organic Chemistry" by TW Greene and PGM utts, 2nd ed., 1991, Wiley NY) before the critical step, applying methods well known in the art. These protective groups can be eliminated at a later stage of the synthesis, applying standard methods described in the technical literature. If the compounds (II) or (IX) and / or the alcohols (VIII) contain chiral centers, the pyridopyrimidinones (I) may be obtained in the form of mixtures of diastereomers or enantiomers, which may be separated by methods well known in the art. , eg HPLC (chiral) HPLC or crystallization. The racemic compounds can be separated eg into their antipodes via the diastereomeric salts by crystallization with optically pure acids or by separation of their antipodes by applying specific chromatographic methods using a chiral adsorbent or a chiral eluent. Reaction scheme E: Obtaining the carboxylic acids used in reaction schemes A and B (1) II III The xynoic acids (III) (in which m? 0) can be obtained in the manner described in reaction scheme E: a chloronoic acid (II) is reacted with an alcoholate in a suitable solvent, for example DMF, THF or mixtures of them, for example at an elevated temperature. The alcoholate can be obtained by treating the corresponding alcohol with a suitable base, for example NaH or KOtBu. After separation, which is suitable for weakly acid organic substances, alkoxyalkanoic acids (III) are usually obtained in a sufficiently pure form to be used in the next step without further purification. The compounds (III) can be obtained in the form of mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, eg HPLC (chiral) or crystallization. The racemic compounds can be separated, for example, into their antipodes by the diastereomeric salts by crystallization with optically pure amines, for example (R) - or (S) -1-phenyl-ethylamine, (R) - or (S) - 1-naphthalene-1-yl-ethylamine, brucine, quinine or quinidine or by separation of their antipodes by specific chromatographic methods, using a chiral adsorbent or a chiral eluent. Optionally, the compounds (III) can be synthesized by applying a stereoselective method, which is well known to those skilled in the art. Reaction scheme F: Obtaining the carboxylic acids used in reaction schemes A and B (2) II III IV V The 5-aryl-pentanoic acids (V), which are substituted in the 2-position by hydrogen, an alkyl chain or a fluorinated alkyl chain, can be obtained by the method represented in the reaction scheme F: in a first step a a suitably substituted (II) deprotonated malonate is reacted (R is eg Me, Et, Bn or another suitable protective group, described eg in "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) with triphenylphosphonium bromide and an aryl-aldehyde (substituted) in a suitable solvent, for example DMF or DMSO, typically at elevated temperature. The substituted malonates (II) are easily obtained, as they are commercial products or by well-known methods, and are easily deprotonated using a suitable base, for example NaH, KOtBu, NaOMe or NaOEt, in a suitable solvent, for example ether of diethyl or THF. The product (III) can be recovered from the reaction mixture by customary separation operations, including a purification step, for example by column chromatography. The 2- (3-aryl-allyl) -malonic esters substituted in the 2 (III) position can be reduced to the corresponding esters of 2- (3-aryl-propyl) -malonic acid (IV) in a suitable solvent, for example methanol, ethanol or EtOAc, under a hydrogen atmosphere, and with a suitable catalyst, for example palladium on carbon (step b). Once the reaction is complete, filtration and evaporation of the solvent may be sufficient to obtain the product (IV) in pure form. The substituted 5-aryl-pentanoic acids in position 2 (V) can be obtained from the compounds (IV) by a step which is usually known as "saponification / decarboxylation" (step c): the compound IV is heated together with an alkaline hydroxide, for example potassium, sodium or lithium hydroxide, in a suitable solvent, for example ethanol. Depending on the nature of R, a two-step process may be appropriate: i) removal of the ester protecting group (as described, for example, in "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) and ii) decarboxylation, the compounds (V) being obtained. After evaporation of the solvent, a suitable separation of weakly acidic organic substances and a purification step for recovering the substituted 5-aryl-pentanoic acids in the 2-position (V) of the reaction mixture is convenient. Compounds (V) can be obtained in the form of mixtures of erythrocytes or enantiomers, which can be separated by methods well known in the art, eg HPLC (chiral) or crystallization. The racemic compounds can be separated, for example, into their antipodes by the diastereomeric salts by crystallization with optically pure amines, for example (R) - or (S) -1-f-en-1-ethyl-1-amine, (R) - or (S) -l-na ft a 1 en-1-i 1 -eti 1 amine, brucine, quinine or quinidine or by separation of their antipodes by specific chromatographic methods, using a chiral adsorbent or a chiral eluent. Optionally, the compounds (V) can be synthesized by a stereoselective method, applying techniques well known to those skilled in the art.

Reaction scheme G: Obtaining the carboxylic acids used in reaction schemes A and B (3) ROOC IV V The 4-alkyl- or 4-fluoroalkyl-5-aryl-pentanoic acids (V) can be obtained in the manner described in scheme G: in a first step a, which is usually known as the ittig reaction, a suitable base is added, for example KOtBu or sodium ethanolate, to an aryl triphenyl phosphonium salt (Wittig salt) in a suitable solvent, for example ethanol or THF. The mixture is stirred for some time at an appropriate temperature to allow the formation of the well-known "ilide" intermediate of the Wittig reaction, then the ethyl levulinate or an appropriately substituted? -aceto acid (II) is added to the mixture ( R is eg Me, Et, Bn or another suitable protective group, described eg in "Protective Groups in Organic Chemistry" of T.W. Greene and P.G.M. Wutts, 2nd ed. , 1991, Wiley N.Y.) and the mixture is maintained at a temperature that will depend on the nature of the Wittig reagent that has been used. Compound III is recovered from the reaction mixture after the usual separation and purification steps, for example by column chromatography. In the next step b, the obtained alkeneic acid ester (III) can be reduced under a hydrogen atmosphere, with a catalyst, for example palladium on carbon, in a solvent of the ethanol or EtOAc type. Filtration and evaporation of the solvent may be sufficient to obtain the product (IV) in pure form. In the saponification step c the obtained compound IV can be saponified with an alkaline hydroxide, in a suitable solvent, for example potassium, sodium or lithium hydroxide in solvents of the ethanol, methanol or THF type or mixtures thereof, obtaining an -alkyl- or 4-fluoroalkyl-5-aryl-pentanoic acid (V) after a separation which is suitable for weakly acidic organic substances. Depending on the nature of R, an alternative method for breaking ester (IV) (see eg "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) may be appropriate. . The compounds (V) can be obtained in the form of mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, eg HPLC (chiral) or crystallization. The racemic compounds can be separated, for example, into their antipodes by the diastereomeric salts by crystallization with optically pure amines, for example (R) - or (S) -1-phenylethylamine, (R) - or (S) - 1-naphthalene-1-yl-ethylamine, brucine, quinine or quinidine or by separation of their antipodes by specific chromatographic methods, using a chiral adsorbent or a chiral eluent. Optionally, the compounds (V) can be synthesized by a stereoselective method, applying techniques well known to those skilled in the art. Reaction scheme H: Obtaining the carboxylic acids used in reaction scheme A and B (4) The aryloxy-alkanoic acids (IV) (in which m? 0) can be obtained in the manner described in the reaction scheme H: in a first step a is added an appropriate base, for example sodium ethanolate, sodium methanolate or KOtBu, a a phenol suitably substituted with phenol and the ethyl chloroalkanoate (II) in a solvent of the ethanol type (R is, for example, Me, Et, Bn or another suitable protective group, described, for example, in "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, iley NY). Once the reaction, which can be carried out at an elevated temperature, is completed, the mixture is separated and purified in the usual manner. After evaporation of the solvent a residue is obtained, from which the product (III) can be isolated, for example by column chromatography. In the next step b the aryloxy-alkanoic acid ester obtained is saponified, for example by treatment with an alkali hydroxide, for example potassium, sodium or lithium hydroxide, in a suitable solvent, for example ethanol, methanol or THF or mixtures of the same. The separation and purification should be appropriate for weakly acidic organic substances, obtaining from them the aryloxy-alkanoic acids (IV). Depending on the nature of R, an alternative procedure for breaking ester (III) (see eg "Protective Groups in Organic Chemistry" by TW Greene and PGM Wutts, 2nd ed., 1991, Wiley NY) may be appropriate. . The compounds (IV) can be obtained in the form of mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art, eg HPLC (chiral) or crystallization. The racemic compounds can be separated, for example, into their antipodes by the diastereomeric salts by crystallization with optically pure amines, for example (R) - or (S) -1-phenylethylamine, (R) - or (S) - 1-naphthalene-1-yl-ethylamine, brucine, quinine or quinidine or by separation of their antipodes by specific chromatographic methods, using a chiral adsorbent or a chiral eluent. Optionally, the compounds (IV) can be synthesized by a stereoselective method, applying techniques well known to those skilled in the art. The corresponding salts can be obtained with acids by applying standard methods, known to those skilled in the art, for example, the compound of formula (I) is dissolved in an appropriate solvent, for example dioxane or THF, and a suitable amount of the corresponding acid is added. The products can be isolated normally by filtration or chromatography. The conversion of a compound of the formula (I) to a pharmaceutically acceptable salt with a base can be carried out by treating the compound with the base. A possible method of obtaining a salt consists, for example, in the addition of 1 / n equivalents of a basic salt, for example, for example M (OH) n, where M = a metal or ammonium cation and n = number of hydroxide anions, to a solution of the compound in a suitable solvent (e.g., ethanol, ethanol-water mixture, tetrahydrofuran-water mixture) and removal of the solvent by evaporation or lyophilization. The conversion of the compounds of the formula (I) to pharmaceutically acceptable esters can be carried out, for example, by treatment of an appropriate carboxy group, present in the molecule, with a suitable alcohol, using, for example, a condensation reagent. , for example benzotriazole-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate (BOP), N, N-dicylohexylcarbodiimide (DCC), N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride (EDCI) or O- (1, 2-dihydro-2-oxo-l-pyridyl) -?,?,?,? - tetra-methyluronium tetrafluoroborate (TBTU). The pharmaceutically acceptable esters can also be obtained by treatment of a suitable hydroxy group, present in the molecule, with an appropriate acid, optionally or if necessary in the presence of a condensing agent, already mentioned above. In the event that their preparation is not described in the examples, the compounds of the formula (I) and all the intermediates can be obtained by similar methods or according to the methods already described above. The starting materials are commercial products or compounds already known in the art. As mentioned before, the compounds of the formula (I) of the present invention can be used as medicaments for the treatment and / or prevention of diseases are modulated with HM74A agonists. Examples of such diseases are elevated levels of lipids and cholesterol, especially dyslipidemia, low HDL cholesterol, atherosclerotic diseases, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, in particular diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, sepsis, inflammatory diseases (for example asthma, arthritis, colitis, pancreatitis, cholestasis / fibrosis of the liver and diseases that have an inflammatory component, for example Alzheimer's disease or disturbed / improbable cognitive function). The use as a medicament for the treatment of atherosclerosis, the low levels of HDL cholesterol, the non-insulin dependent diabetes mellitus and the metabolic syndrome is preferred. The invention also relates to pharmaceutical compositions containing a compound described above and a pharmaceutically acceptable carrier and / or adjuvant. The invention further relates to compounds described above for use as therapeutically active substances, especially as therapeutically active substances for the treatment and / or prevention of diseases that are modulated with HM74A agonists, in particular as therapeutically active substances for the treatment and / or prevention of high lipid levels, high cholesterol levels, atherosclerotic diseases, dyslipidemia, low HDL cholesterol, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, disturbed or unlikely cognitive function, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver.

In another embodiment, the invention relates to a method for the treatment and / or prevention of diseases that are modulated with HM74A agonists, in particular for the treatment and / or prevention of high levels of lipids, high cholesterol levels, diseases atherosclerotic, dyslipidemia, low HDL cholesterol, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, disturbed or improbable cognitive function, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver, the method consists of administering a compound described above to a human being or an animal. The invention also relates to the use of compounds defined above for the treatment and / or prevention of diseases that are modulated with HM74A agonists, in particular for the treatment and / or prevention of high levels of lipids, high cholesterol levels, diseases atherosclerotic, dyslipidemia, low HDL cholesterol, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, disturbed or unlikely cognitive function, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver. The invention also relates to the use of the compounds described above for the manufacture of medicaments for the treatment and / or prevention of diseases that are modulated with HM74A agonists, in particular for the treatment and / or prevention of high levels of lipids, levels High cholesterol, atherosclerotic diseases, dyslipidemia, low HDL cholesterol, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome , Alzheimer's disease, Parkinson's disease, schizophrenia, disturbed or improbable cognitive function, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver. Such medications contain a compound already described in previous pages. The prevention and / or treatment of atherosclerosis, low levels of HDL cholesterol, diabetes mellitus not dependent on insulin and the metabolic syndrome are preferred.

The following tests are carried out in order to determine the biological activity of the compounds of the formula (I). Primary test for radiolabeled ligand competition binding Nicotinic acid binding assays are performed with membrane preparations. A pellet of cells containing 1 x 108 HEK-293 cells, stably transfected with the HM74A receptor, is resuspended in 3 ml of ice-cooled Dounce buffer (10 mM Tris-Cl, pH = 7.6, 0.5 mM gCla) supplemented with a cocktail of Roche protease inhibitor and homogenized at high speed in a Polytron type homogenizer twice for 20 s on ice. After the addition of 1 ml of tonicity restoration buffer (10 mM Tris, pH = 7.6, 0.5 mM MgCl2, 600 mM NaCl), the nuclei and non-disintegrated cells are separated by centrifugation at 1,000 rpm for 5 min. The homogenized material is centrifuged at 60,000 rpm for 30 min and the pellets are resuspended in Tris buffer (50 mM Tris, pH = 7.4, containing protease inhibitors). Mixtures of binding reactions contain 20 g of membranes determined by the BCA protein assay (Pierce), 50 nM of nicotinic acid- [H3] (Amersham) with or without compound addition in 250 μ? of fixation buffer (50 mM Tris, pH = 7.4, 2 mM MgCl2, 0.02% CHAPS). Incubations are carried out at room temperature for 2 h and are terminated by filtration using a Filtermate Harvester apparatus (PerkinElmer) on GF / C filter plates (Millipore). The nicotinic acid [H3] fixed by scintillation counting is determined in a Top Count NXT type apparatus (PerkinElmer). The compounds are dissolved in a concentration of 10 ~ 2 or 10 ~ 3 M in DMSO, subsequent dilutions are made in the binding buffer. The effects of the compounds are expressed in the form of% inhibition of the binding of nicotinic acid- [H3]. The sigmoidal curves are adjusted using the XLfit3 software (ID Business Solutions Ltd. UK) and the values of the IC50 are determined. The compounds of the present invention have IC 50 values comprised between 0.001 μ? and 100 μ in the fixation assay. Preferably, the compounds of the present invention have IC50 values comprised between 0.001 μ? and 10.0 μ, more preferably between 0.001 μ? and 1 μ ?. Secondary assay of calcium fluoride indicator (FLIPR) HEK-293 cells are cultured in a tissue culture medium (DMEM / Nut mix F12 Medium with Glutamax I (Invitrogen), containing 10% FBS) at 37 ° C in an atmosphere containing 5% C02. These cells are cultured in plates of 6 well plates of 3xl05 cells / well and are transfected twice with DNA vectors (pcDNA3.1, Invitrogen) expressing HM74A or H 74 and chimeric Gqi9 protein G. Two days after transfection, the contents of the wells are combined and spread in 150 cm2 flasks, in the presence of 50 μ? / P? of hygromycin (Invitrogen) and 500 ug / ml of geneticin (Gibco). Fourteen days after extension, colonies are extracted, expanded and their expression is analyzed by performing a functional assay (FLIPR). The HEK-293 cells stably transfected in HM74A or HM74 and the Gqi9 chimeric G protein are plated at 50,000 cells / well in 96-well transparent bottom black plates (Costar) and grown to confluence overnight. in a culture medium (DMEM / Nut mix F12 Medium with Glutamax I (Invitrogen), containing 10% FBS) at 37 ° C in a humidified cell incubator containing 5% C02. The culture media is aspirated and replaced with 100 μ? of IX dye of the FLIPR Calcium Assay Dye type (Molecular Devices) in Hank's balanced salt solution (HBSS) containing 10 mM HEPES and 250 mM probenecid (Sigma), at 37 ° C for 1 hour. Transfer the plates with the cells to a FLIPR unit (Molecular Devices) and add 50 μ? of 3x compound solution. Fluorescence emissions are measured and the effects of the compounds are expressed as% stimulation of the maximum response of nicotinic acid (100 μ?). The sigmoidal curves are adjusted using the XLfit3 software (ID Business Solutions Ltd. UK) and the EC50 values are determined. The compounds of the present invention possess EC50 values comprised between 0.001 μ? and 100 μ? in the FLIPR trial. Preferably, the compounds of the present invention have EC50 values between 0.001 μ and 10.0 μ?; more preferably between 0.001 μ? and 1 μ ?. The EC50 values of some compounds of the present invention are reported in the following table.

The compounds of the formula I and / or their pharmaceutically acceptable salts can be used as medicaments, for example in the form of pharmaceutical preparations for enteral, parenteral or topical administration. They can be administered, for example, perorally, eg in the form of tablets, coated tablets, dragees, hard or soft gelatine capsules, solutions, emulsions or suspensions, rectally, eg in the form of suppositories, parenterally, eg in the form of injectable solutions or suspensions or solutions for infusion, or topically, eg in the form of ointments, creams or oils. Oral administration is preferred.

The production of the pharmaceutical preparations can be carried out in a manner that will be familiar to any person skilled in the art, which consists in incorporating the described compounds of the formula I and / or their pharmaceutically acceptable salts, optionally in combination with other therapeutically valuable substances, into a form of galenic administration together with solid or liquid carrier materials, suitable, non-toxic, inert, therapeutically compatible, and, if desired, with the usual pharmaceutical adjuvants. The ideal carrier materials are not only the inorganic carrier materials, but also the organic carrier materials. For example, lactose, corn starch and its derivatives, talc, stearic acid and its salts can be used as carrier materials for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carrier materials for soft gelatine capsules are, for example, vegetable oils, waxes, fats and semisolid and liquid polyols (however, depending on the nature of the active ingredient, the use of carriers may not be necessary. in the case of soft gelatine capsules). The suitable carrier materials for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar and the like. The suitable carrier materials for the injectable solutions are, for example, water, alcohols, polyols, glycerin and vegetable oils. The suitable carrier materials for suppositories are, for example, natural or hydrogenated oils, waxes, fats and semi-liquid and liquid polyols. Suitable carrier materials for topical preparations are glycerides, semi-synthetic and synthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins, liquid fatty alcohols, sterols, polyethylene glycols and cellulose derivatives. As pharmaceutical adjuvants, the usual stabilizers, preservatives, humectants and emulsifiers, the agents that improve the consistency, the aroma, the salts for varying the osmotic pressure, the buffer substances, the solubilizers, the dyes and the masking agents are taken into consideration. the antioxidants. The dosage of the compounds of the formula I can vary within wide limits depending on the disease to be controlled, the age and the individual health status of the patient and the mode of administration and will obviously have to be adjusted to the individual requirements in each particular case . For adult patients, a daily dose of 1 to 5000 mg, preferably 1 to 1000 mg, especially 1 to 300 mg, is taken into consideration. Depending on the dosage it is convenient to administer the daily dose divided into several dosage units, eg in 1-3 dosage units. The pharmaceutical preparations conveniently contain from 1 to 1000 mg, preferably from 1 to 300 mg, more preferably from 1 to 100 mg of a compound of the formula I. The following illustrative examples serve to describe the present invention in greater detail. However, in no way is it intended to limit the scope of the same. Ex emplos Abbreviations AcOH = acetic acid, Boc20 = ditert-butyl dicarbonate, BOP-C1 = bis (2-oxo-3-oxazolidinyl) phosphonic chloride, nBuLi = n-butyl-lithium, CH2C12 = dichloromethane, CH3CN = acetonitrile, DI PEA = N, N- diisopropylethylamine, DMF = N, -dimethylformamide, DMSO = dimethyl sulfoxide, DMAP = N, N-dimethylaminopyridine, EtOH = ethanol, EDCI = N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride, EtOAc = ethyl acetate , Et20 = diethyl ether, h = hour, HC1 = hydrochloric acid, HOBt = 1-hydroxybenzo-triazole, KOH = potassium hydroxide, KOtBu = potassium tert-butylate, LiH DS = lithium hexamethyldisilazide, MeOH = methanol, min = minutes , NaH = sodium hydride, Na2S04 = sodium sulfate, NH4C1 = ammonium chloride, NMM = N-methylmorpholine, iPrOH = isopropanol, rend. quant. = quantitative yield, t.amb. = room temperature, KOH = potassium hydroxide, TBME = methyl ether and tert-butyl, TBTU tetrafluoroborate 0- (benzotriazol-1-yl) -?,?,? ' ,? ' -tetramethyluronium, THF = tetrahydrofuran, TFA = trifluoroacetic acid. General observations The reactions are carried out under an argon atmosphere, when it is considered appropriate. Example 1 2-Benzyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one 1.1 The 2-amino-nicotinamide [13438-65-8] is obtained from 2-amino-3-cyanopyridine [24517] -64-4] according to the procedure described by EC Taylor and A.J. Crovetti, J. Org. Chem. 19 (10) pp. 1633 - 1640, 1954; MS (m / e) = 137.1 [M +]. 1.2 To a suspension of 2-amino-nicotinamide (100 mg, 0.7 min) in THF (5 mL), benzyloxyacetyl chloride [19810-31-2] (127 μ ?, 0.8 mmol) is added dropwise at 5 ° C. ) in THF (2 mi). The reaction mixture is heated at reflux for 2 hours. Water is added, the phases are separated and the inorganic phase is extracted with EtOAc (3 times). The organic phases are combined, washed with brine, dried over Na 2 SO 4, filtered and concentrated in vacuo. Column chromatography on silica gel using a 9: 1 mixture of CH 2 Cl 2: MeOH 9: 1 gives 2- (2-benzyloxy-acetylamino) -nicotinamide (76 mg, 36%), MS (m / e) = 286.1 [M + H +]. 1.3 2- (2-Benzyloxy-acetylamino) -nicotinamide (76 mg, 0.3 mmol) in H20 / EtOH (4 mL, 1: 1) is stirred under reflux for 2 hours with sodium carbonate (28 mg, 0.3 mmol). Water is added, the phases are separated and the inorganic phase is extracted with EtOAc (3 times). The organic phases are combined, washed with brine, dried over Na 2 SO 4, filtered and concentrated in vacuo to obtain 2-benzyloxymethyl-3 H -pyrido [2,3-d] pyrimidin-4-one (15 mg, 21 mg). %) in the form of white solid, MS (m / e) = 268.1 [M +]. Example 2 2-Phenoxymethyl-3H-pyrido [2,3-d] pyrimidin-4 -one In a similar manner to Examples 1.2-1.3, starting with 2-amino-nicotinamide [13438-65-8] and phenoxyacetyl [701-99-5] yields 2-phenoxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one as a white solid, MS (m / e) = 254.1 [M + H +]. Example 3 2- (4-Allo-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one Similar to Examples 1.2-1.3, from 2-amino-nicotinamide [13438-65] -8] and 4-chloro-phenoxyacetyl chloride [4122-68-3] give 2- (4-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one as a solid. slightly yellow, MS (m / e) = 288.1 [M + H +, 1C1]. Example 4 2- (5-phenyl-pentyl) -3H-pyrido [2,3-d] pyrimidin-4-one 4.1 A solution of 6-phenylhexanoic acid [5581-75-9] (1.45 g, 7.6 mmoles) is treated. ) in CH2Cl2 (15 mL) with oxalyl chloride (0.72 mL, 8.6 mmol) in the presence of a catalytic amount of DMF. The solution is stirred at room temperature for 2 h. The solvent is evaporated, yielding the crude 6-phenylhexanoic acid chloride, which is used without further purification for the next step. 4.2 To the 2-amino-3-cyanopyridine [24517-64-4] (200 mg, 1.7 mmol) in CH2Cl2 (3 mL) and pyridine (3 mL) is added a solution of the 6-phenylhexanoic acid chloride (1.5 eq.) in CH2C12 (1 mL) and the reaction mixture is stirred at room temperature overnight. Water is added, the phases are separated and the pH of the inorganic phase is adjusted (pH 7). The inorganic phase is extracted with EtOAc (3 times), the organic phases are combined, washed with brine, dried with Na 2 SO 4, filtered and concentrated in vacuo. Trituration in diethyl ether gives 6-phenyl-hexanoic acid (3-cyano-pyridin-2-yl) -amide, 360 mg (73%) as a white solid, MS (m / e) = 294.3 [M + H +]. 4. 3 To the 6-phenyl-hexanoic acid (3-cyano-pyridin-2-yl) -amide (360 mg, 1.2 mmol) in sodium hydroxide (6 ml, 5) is added ethanol (0.1 ml) and hydrogen peroxide. hydrogen (3% in H20, 1.5 ml). The reaction mixture is heated at reflux for 3 hours. Water is added, the solution is acidified (pH 5) and extracted with EtOAc (3 times). The organic phases are combined, washed with brine, dried over Na 2 SO, filtered and concentrated in vacuo. By column chromatography through silica gel with a 9: 1 mixture of CH2C12: eOH as eluent and subsequent trituration in diethyl ether, 2- (5-phenyl-pentyl) -3H-pyrido [2, 3] is obtained. d] pyrimidin-4-one as a white solid, MS (m / e) = 294.3 [M + H +]. Example 5 2- (4-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one Similarly to Examples 4.2-4.3, 4-methoxy-phenoxy-acetic acid [42082-29-1] and 2-amino-3-cyanopyridine [24517-64-4] are obtained from the chloride. - (4-methoxy-1-phenox ime ti 1) - 3H-pi rido [2, 3 -d] pi rimidinone -one as a white solid, MS (m / e) = 284.0 [M + H +]. EXAMPLE 6 2- (4-Ethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one Similar to Examples 4.2-4.3, from (4-ethylphenoxy) acetyl chloride [167762] -94-9] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (4-ethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one in the form of white solid, MS (m / e) = 282.3 [M + H +]. Example 7 2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one. Similarly to Examples 4.2-4.3, from 5-phenylvaleryl chloride [20371-41-] 9] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one as a white solid , MS (m / e) = 280.3 [M + H +]. EXAMPLE 8 2- (4-Fluoro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one. Similar to Examples 4.2-4.3, from (4-fluorophenoxy) -acetyl chloride [ 405-78-7] and 2-amino-3-cyanopyridine [24517-64-4] yield 2- (4-fluoro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one in solid white form, MS (m / e) = 272.0 [M + H +]. EXAMPLE 9 2- (3-Chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one 9.1 In a manner similar to that described in example 4.2, starting from 3-chloro-phenoxyacetyl chloride [114476 -84-5] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (3-chloro-phenoxy) -N- (3-cyano-pyridin-2-yl) -acetamide in the form of slightly brown solid, MS (m / e) = 288.0 [M + H +, 1C1]. 9. 2 In a manner similar to that described in Example 4.3, starting with 2- (3-chloro-phenoxy) -N- (3-cyano-pyridin-2-yl) -acetamide gives 2- (3-chloro- phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one as a white solid, MS (m / e) = 287.9 [M + H +, 1C1]. EXAMPLE 10 2-phenethyl-3H-pyrido [2,3-d] pyrimidin-4 -one Similar to Examples 4.2-4.3, from benzenepropanoyl chloride [645-45-4] and 2-amino-3 -cyanopyridine [24517-64-4] yields 2-phenethyl-3H-pyrido [2,3-d] pyrimidin-4-one as a slightly yellow solid, MS (m / e) = 252.1 [M + H + ] EXAMPLE 11 2- [2- (3-Chloro-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidin-4-one In a manner similar to Examples 4.2-4.3, starting with (3-chlorophenyl) propanoyl [40478-50-0] and 2-amino-3-cyanopyridine [24517-64-4] yields 2- [2- (3-chloro-phenyl) -ethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one as a white solid, MS (m / e) = 286.0 [M + H +, 1C1]. EXAMPLE 12 2- [2- (3-methoxy-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidin-4-one. Similarly to Examples 4.2-4.3, starting with the 3- (3-methoxyphenyl) propionyl [40478-49-7] and 2-amino-3-cyanopyridine [24517-64-4] gives 2- [2- (3-methoxy-phenyl) -ethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one as a white solid, MS (m / e) = 282.0 [M + H +]. EXAMPLE 13 2- [4- (4-Chloro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4 -one. Similar to Examples 4.2-4.3, starting with (4-chloro-phenyl) -pentanoyl [61875-54-5] and 2-amino-3-cyanopyridine [24517-64-4] gives 2- [4- (4-chloro-phenyl) -butyl] - 3H-pyrido [2, 3-d] pyrimidin-4-one as a white solid, MS (m / e) = 314.0 [M + H +, 1C1]. EXAMPLE 14 2- (6-phenyl-hexyl) -3H-pyrido [2,3-d] pyrimidin-4-one In a manner similar to that described in examples 4.2-4.3, from 7-phenylheptanoyl chloride [61875- 55-6] and 2-amino-3-cyanopyridine [24517-64-4] yield 2- (6-phenyl-hexyl) -3H-pyrido [2,3-d] pyrimidin-4-one as a colorless oil, MS (m / e) = 307.2 [M +]. Example 15 2- [4- (4-Fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one. Similar to Examples 4.2-4.3, from (4-fluorophenyl) pentanoyl [204589-92-4] and 2-amino-3-cyanopyridine [24517-64-4] yields 2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one as a white solid, MS (m / e) = 298 [M + H +]. Example 16 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one Similar to Examples 4.2-4.3, from (2-methoxyphenoxy) acetyl chloride [40926 -73-6] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one in the form of white solid, MS = 283.9 [M + H +]. Example 17 2-p-Tolyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one Similar to Examples 4.2-4.3, from (4-methylphenoxy) acetyl chloride [15516-47-9] ] and 2-amino-3-cyanopyridine [24517-64-4] yields 2-p-tolyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one as a white solid, EM = 268.2 [ M + H +]. EXAMPLE 18 2- (2-Elo-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one Similar to Examples 4.2-4.3, from (2-chlorophenoxy) acetyl chloride [20143 -41-3] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (2-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one in the form of white solid, MS = 287.9 [M + H +, 1C1]. EXAMPLE 19 2- (2,3-Dimethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4 -one. Similar to Examples 4.2-4.3, from (2,3-dimethylphenoxy) chloride Acetyl [40926-74-7] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (2,3-dimethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidine -4 -one as a white solid, MS (m / e) = 282 [M + H +]. EXAMPLE 20 2- (Naphthalen-1-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin -one In a similar manner to Examples 4.2-4.3, from (naphthalene-1-yloxy) -acetyl chloride [2007-12-7] and 2-amino-3-cyanopyridine [24517-64-4] give 2- (naphthalen-1-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one in the form of a matt white solid, MS (m / e) = 304 [M + H +]. EXAMPLE 21 2- (4-Chloro-2-methyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one In a manner similar to Examples 4.2-4.3, from (2-methyl) chloride -4-chlorophenoxy) acetyl [6597-79-1] and 2-amino-3-cyanopyridine [24517-64-4] yield 2- (4-chloro-2-methyl-phenoxymethyl) -3H-pyrido [2 , 3-d] pi.rimidin-4-one as a white solid, MS (m / e) = 301.9 [M + H +, 1C1]. EXAMPLE 22 6-Methyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4 -one. Similar to Examples 4.2-4.3, from 5-phenylvaleryl chloride [ 20371-41-9] and 2-amino-5-methylnicotinonitrile [38076-78-7] give 6-methyl-2- (phenyl-butyl) -3H-pyrido [2,3-d] pyrimidine-4 -one in the form of white solid, MS (m / e) = 294.1 [M + H +]. Example 23 (4-Oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester. Similar to Examples 4.2-4.3, from benzyloxycarbonylaminoacetyl chloride [15050- 24-5] and 2-amino-3-cyanopyridine [24517-64-4] yield (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamate from benzyl in the form of a matt white solid, MS (m / e) = 311 [M + H +]. Example 24 N- (4-Oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide 24.1 Stir at room temperature for 2 h (4-oxo- 3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester (383 mg, 1.23 mmol) in HBr (33% in acetic acid, 4 mL). The TBME (15 ml) is added, the precipitated solid is filtered and washed with TBME, obtaining a salt of 2-aminomethyl-3H-pyrido [2]., 3-d] pyrimidin-4-one (0.1 CH3C02H, 2.03 HBr) as a white solid, MS = 176 [M +], which is used for the next reaction without further purification. 24.2 To the 3-phenylpropionic acid [501-52-0] (66.6 mg, 0.444 mmol) in DMF (4 mL) is added at 0 ° C EDCI [25952-53-8] (102 mg, 0.532 mmol) , HOBt [2592-95-2] (8 mg, 0.059 mmol) and NMM [109-02-4] (0.15 ml, 1.18 mmol). The reaction mixture is stirred at room temperature for 2 h and then added to a solution of the salt of 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (CH3C02H, HBr) (100 mg). in DMF (2 ml). Stirring is continued for 18 h, the solvents are evaporated and the residue is redissolved in EtOAc / THF and a saturated solution of ammonium chloride. The inorganic phase is extracted with EtOAc. The organic phases are combined, washed with brine, dried over Na 2 SO 4, filtered and concentrated. Column chromatography with a 9: 1 mixture of CH2Cl2 / MeOH and subsequent trituration with TBME yields N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) - 3-phenyl-propionamide (43.1 mg, 47%) as a white matt solid, MS (m / e) = 309 [+ H +]. EXAMPLE 25 N- (4-Oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -4-phenyl-butyramide In a manner similar to that described in example 24.2, from acid 4 phenylbutyric [1821-12-1] and 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one, N- (4 -oxo-3,4-dihydro-pyrido [2,3] is obtained -d] pyrimidin-2-ylmethyl) -4-phenyl-butyramide as a pink solid, MS (m / e) = 323.3 [M + H +]. Example 26 6-Bromo-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one. Similarly to Examples 4.2-4.3, from 5-phenylvaleryl chloride [ 20371-41-9] and 2-amino-5-bromonicotinonitrile [709652-82-4] gives 6-bromo-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidine- 4-one as a white solid, MS (m / e) = 357.9 [M + H +, lBr]. Example 27 6-Bromo-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one. Similarly to Examples 4.2-4.3, starting from 5- (4-Fluorophenyl) pentanoyl chloride [204589-92-4] and 2-amino-5-bromonicotinonitrile [709652-82-4] yields 6-bromo-2- [4- (4-fluoro-phenyl) ) -butyl] -3H-pyrido [2,3-d] pyrimidin-4 -one as a white solid, MS (m / e) = 376.1 [M + H +, lBr]. Example 28 2- [3- (4-Methoxy-phenyl) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one In a glass tube fitted with a screw cap, the 3- (4- methoxyphenyl) -1-propanol ([5406-18-8], 137 mg, 0.826 mmol) to a mixture of 2-chloropyrido [2,3-d] pyrimidin-4 (1H) -one ([93049-38-8 ], 50 mg, 0.28 mmole) and KOtBu (62 mg, 0.55 mmole) in DMSO (2 ml). The mixture is heated (120 ° C, 3 days) and the title compound of the product mixture is isolated by reverse phase preparative HPLC (Column Zorbax XdB C18 from Agilent, solvent gradient: CH3CN from 5 to 95% in water with 0.1% TFA in 7 min, flow rate: 30 ml / min). MS m / e = 310.5 [? -? '], NMR-H1 (DMSO-d6) d = 2.02 (dd, 2H), 3.36 (d, 2H), 3.71 (s, 3H), 4.42 (d, 2H) , 6.86 (d, 2H), 7.15 (d, 2H), 7.36 (dd, 1H), 8.38 (d, 1H), 8.79 (d, 1H). Example 29 2- (3-phenyl-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 280.4 [MH "]) in a manner similar to that described in example 28 from the 3-phenyl-1-propanol [122-97-4]. Example 30 2- (4-phenyl-butoxy) -3H-pyrido [2,3-d] pyrimidin-4 -one The title compound is obtained (MS m / e = 294 [MH-]) in a manner similar to that described in Example 28 from 4-phenyl-1-butanol [3360-41-6]. EXAMPLE 31 2- [4- (4-methoxy-phenyl) -butoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 324.5 [MH "] ) in a manner similar to that described in example 28 from 4- (4-methoxyphenyl) -1-butanol [52244-70-9]. Example 32 2- (3-pyridin-3-yl-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 281.4 [MH "]) of similar to that described in Example 28 from 3- (3-pyridyl) -1-propanol [2859-67-8].

EXAMPLE 33 2- (2-phenoxy-ethoxy) -3H-pyrido [2,3-d] pyrimidin-4 -one The title compound is obtained (MS m / e = 282.1 [MH ~]) in a manner similar to that described in Example 28 from 2-phenoxyethanol [122-99-6]. EXAMPLE 34 2- [2- (Naphthalen-2-yloxy) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 332.3 [MH ~] ) in a manner similar to that described in example 28 from 2- (2-naphthoxy) ethanol [93-20-9]. Example 35 2- (3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4 -one The title compound (MS m / e = 296.5 [MH ~]) is obtained in a manner similar to that described in example 28 from the 3-phenoxy-1-propanol [6180-61-6]. Example 36 2-Phenethyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4 -one 36.1 NaH (6.87 g, 172 mmol) is slowly added to a solution of 2-phenylethanol ([60-12-8], 6.00 g, 5.88 ml, 49.1 mmol) in DMF (50 ml). The reaction mixture is heated and maintained at 60 ° C for 10 min. Slowly and carefully add chloroacetic acid ([79-11-8], 8.12 g, 86 mmol) (exothermic reaction) and keep the mixture at 60 ° C for 1 h. The mixture is poured onto ice and extracted twice with diethyl ether. The aqueous phase is acidified (HC1, pH ~ 3) and extracted twice with ethyl acetate. The phenethyloxy-acetic acid [81228-03-7] is obtained after drying (Na2SO4) and evaporating the solvent. The compound is sufficiently pure to be used in the next step without further purification. 36.2 The phenethyloxy-acetic acid (3.89 g, 18.9 mmol) is dissolved in a mixture of 50 ml of dichloromethane and 2.6 ml of DMF. Oxalyl chloride ([79-37-8], 1.76 ml, 20.8 mmol) is added slowly and the mixture is stirred at rt. during one night. After evaporation of the solvent, phenethyloxy-acetyl chloride [221019-38-1] is obtained and is sufficiently pure for the next step. 36.3 Phenethyloxy-acetyl chloride (3.79 g, 6.12 mmol) is added to a solution of 2-amino-3-cyanopyridine ([24517-64-4], 662 mg, 5.56 mmol) and DMAP (67 mg, 0.55 mmol) ) in a mixture of dichloromethane (8 ml) and pyridine (8 ml). After 3 h at t.amb. the solvent is evaporated and the N- (3-cyano-pyridin-2-yl) -2-phenethyloxy-acetamide is isolated from the residue by column chromatography (silica gel, heptane, ethyl acetate, methanol). MS m / e = 282.1 [M + H +], NMR-H1 (DMSO-d6): 2.91 (t, 2H), 3.77 (t, 2H), 4.18 (s, 2H), 7.17 - 7.23 (m, 5H) , 7.47 (dd, 1H), 8.37 (d, 1H), 8.71 (d, 1H), 10.55 (bs, 1H). 36.4 Potassium carbonate (1.22 g, 8.82 mmol), SO SO (0.44 ml) and hydrogen peroxide (0.9 ml of a 30% solution in H2O) are added to a suspension of N- (3-cyano-pyridine-2). -yl) -2-phenethyloxy-acetamide (400 mg, 1.42 mmol) in methanol (6 ml). After 3 h at t.amb. The mixture is taken up in ethyl acetate and washed with a sat. of NH4C1. The solution is dried (Na 2 SO 4) and the solvent is evaporated. The residue was triturated with methyl ether and tert-butyl, obtaining the title compound. MS m / e = 280.4 [? -? '], NMR-H1 (DMSO-d6): 2.91 (t, 2H), 3.78 (t, 2H), 4.45 (s, 2H), 7.17 - 7.22 (m, 5H ), 7.53 (dd, 1H), 8.49 (d, 1H), 8.93 (d, 1H), 12.44 (bs, 1H). EXAMPLE 37 2- [2- (2-Fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 298.4 [MH ~] ) in a manner similar to that described in example 36 from 2- (2-fluoro-phenyl) -ethanol [50919-06-7]. EXAMPLE 38 2- [3- (3, 4-difluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 332.3 [MH ~]) in a manner similar to that described in example 28 from 3,4-difluoro-phenoxy) -propanol.

Example 39 2- [3- (4-methoxy-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained (MS m / e = 326.3 [MH ~] ) in a manner similar to that described in example 28 from 3- (4-methoxy-phenoxy) -propanol [118943-21-8]. Example 40 2- [2- (4-Fluoro-phenyl) -ethoxymethyl] ^ 3 H -pyrido [2,3-d] pyrimidin-4-one 40.1 The N- (3-cyano-pyridin-2-yl) is obtained -2- [2- (4-Fluoro-phenyl) -ethoxy] -acetamide (MS m / e = 300.3 [M + H +]) from [2- (4-fluoro-phenyl) -ethoxy] -acetic acid [81228-04-8] in a manner similar to Examples 36.2 - 36.3. 40.2 Add hydrogen peroxide (3% in H20, 2.8 ml) and ethanol (0.6 ml) to a suspension of N- (3-cyano-pyridin-2-yl) -2- [2- (4-fluorine phenyl) -ethoxy] -acetamide (900 mg, 3 mmol) in 5N NaOH (11 mL) and the mixture is heated to reflux (4h). After cooling the solution, it is diluted with water and acidified (HC1, pH ~ 3). The title compound which has precipitated is filtered off, triturated with methyl ether and tert-butyl and dried. MS m / e = 300.3 [M + H +], NMR-H1 (DMSO-d6): 2.89 (t, 2H), 3.77 (t, 2H), 4.45 (s, 2H), 7.04-7.12 (m, 2H) , 7.28-7.33 (m, 2H), 7.54 (dd, 1H), 8.50 (d, 1H), 8.95 (d, 1H), 12.45 (bs, 1H). Example 41 2- [4- (4-Fluoro-phenyl) -3-methyl-butyl] -3H-pyrido [2,3-d] pyrimidin-4-one 41.1 Sodium ethanolate is added with cooling (0 ° C) (0.836 g, 12 mmol) was added to a solution of 4-fluorobenzyltriphenylphosphonium chloride ([3462-95-1], 5.00 g, 12 mmol) in ethanol, and the mixture was stirred at rt. for 45 min. Ethyl levulinate ([539-88-8], 1.77 g, 12 mmol) is added and the slightly orange mixture is heated to reflux (36 h). After the usual separation, ethyl 5- (4-fluoro-phenyl) -4-methyl-pent-4-enoate is obtained by column chromatography (silica gel, ethyl acetate / hexane) of the reaction mixture. MS m / e = 237.1 [M + H +]. 41.2 A suspension of 10% palladium on carbon (1.00 g) and ethyl 5- (4-fluorophenyl) -4-methyl-pent-4-enoate (1.01 g) is stirred under a hydrogen atmosphere for 2 hrs. Ethanol (20 ml). The reaction mixture is filtered (Dicalite), and the solvent is evaporated. After evaporation of the solvent, ethyl 5- (4-fluoro-phenyl) -4-methyl-pentanoate is obtained; this compound is used in the next step without further purification. MS m / e = 239.3 [M + H +]. 41. 3 Add ethyl 5- (4-fluoro-phenyl) -4-methyl-pentanoate (1.18 g, 5 mmol) to a solution of KOH (1.39 g, 25 mmol) in ethanol (20 mL). After 2 h to t.amb. the solvent is evaporated and the residue is taken up in water, which is basified (KOH) and extracted twice with diethyl ether. After acidification of the aqueous phase (HC1), the product is extracted with ethyl acetate. The organic phase is washed (brine), dried (Na 2 SO 4) and the solvent is evaporated. The resulting 5- (4-fluoro-phenyl) -4-methyl-pentanoic acid is used in the next step without further purification. NMR-H1 (DMSO-d6): 0.85 (d, 3H), 1.48 (m, 1H), 1.71 (m, 2H), 2.34-2.65 (m, 4H), 6.92 (m, 2H), 7.06 (m, 2H). 41.4 5- (4-Fluoro-phenyl) -4-methyl-pentanoic acid (3-cyano-pyridin-2-yl) -amide is obtained from 5- (4-fluoro-phenyl) -4- methyl-pentanoic in a manner similar to Examples 36.2-36.3. MS m / e = 312.3 [M + H +]. 41.5 The title compound is obtained from the 5- (f-fluorophenyl) -4-methyl-pentanoic acid (3-cyano-pyridin-2-yl) -amide in a manner similar to Example 40.2. MS m / e = 312.1 [M + H +]. NMR-H1 (DMSO-d6): 0.87 (d, 3H), 1.60 (m, 1H), 1.77 (m, 2H), 2.60-2.80 (m, 4H), 7.07 (m, 2H), 7.21 (m, 2H), 7.49 (dd, 1H), 8.45 (d, 1H), 8.91 (d, 1H).

Example 42 2- [5- (4-chloro-phenyl) -pentyl] -3H-pyrido [2,3-d] pyrimidin-4 -one 42.1 The (3-cyano-pyridin-2-yl) -amide is obtained of 6- (4-chloro-phenyl) -hexanoic acid from 6- (4-chloro-phenyl) -hexanoic acid [161725-12-8] in a manner similar to Examples 36.2-36.3. MS m / e = 328.3 [M + H +]. 42.2 The title compound is obtained from 6- (4-chloro-phenyl) -hexanoic acid (3-cyano-pyridin-2-yl) -amide in a manner similar to Example 40.2. MS m / e = 328.1 [M + H +]. EXAMPLE 43 2- [3- (4-Fluoro-phenoxy) -propyl] -3H-pyrido [2, 3-d] pyrimidin-4-one 43.1 Sodium ethanolate (2.18 g, 32 mmol) is added with cooling (0 ° C) to a mixture of 4-fluorophenol ([371-41-5], 3.00 g, 27 mmoles), ethyl 4-chlorobutyrate ([3153-36-4], 4.84 g, 32 mmol) and ethanol (15 ml) and the reaction mixture is boiled at reflux overnight. The solvent is evaporated, the residue is taken up in ethyl acetate and washed with water. After drying (Na 2 SO 4), the solvent is evaporated and ethyl 4- (4-fluoro-phenoxy) -butyrate is isolated from the residue by column chromatography (silica gel, ethyl acetate / heptane). NMR-H1 (DMSO-d6): 1.29 (t, 3H), 2.11 (tt, 2H), 2.51 (t, 2H), 3.96 (t, 2H), 4.13 (q, 2H), 6.79 -6.85 (m, 2H), 6.92-6.99 (m, 2H). 43.2 4- (4-Fluoro-phenoxy) -butyric acid is obtained from ethyl 4- (4-fluoro-phenoxy) -butyrate in a similar manner to Example 41.3. NMR-H1 (DMSO-d6): 2.10 (tt, 2H), 2.59 (t, 2H), 3.97 (t, 2H), 6.79-6.84 (m, 2H), 6.92-6.99 (m, 2H). 43.3 N- (3-Cyano-pyridin-2-yl) -4- (4-fluoro-phenoxy) -butyramide is obtained from 4- (4-fluoro-phenoxy) -butyric acid in a similar manner to the examples 36.2 - 36.3. MS m / e = 300.3 [M + H +]. 43.4 The title compound is obtained from N- (3-cyano-pyridin-2-yl) -4- (4-fluoro-phenoxy) -butyramide in a manner similar to Example 40.2. MS m / e = 300.3 [M + H +]), NMR-H1 (DMSO-d6): 2.16 (tt, 2H), 2.75 (t, 2H), 4.02 (t, 2H), 6.91-6.99 (m , 2H), 7.30-7.34 (m, 2H), 7.31 (dd, 1H), 8.37 (d, 1H), 8.77 (d, 1H). EXAMPLE 44 2- [2- (4-Chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (4-chloro-phenyl) ) -ethanol [1875-88-3] in a manner similar to example 36. MS m / e = 316.1 [M + H +]. Example 45 2- (2-p-tolyl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2-p-tolyl-ethanol [699-02- 5] similarly to example 36. MS m / e = 296.4 [M + H +]. EXAMPLE 46 2- [2- (4-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (4-methoxy-phenyl) ) -ethanol [702-23-8] in a manner similar to example 36. MS m / e = 312.1 [M + H +]. EXAMPLE 47 2- (2-Benzyloxy-ethyl) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 3-benzyloxy-propionic acid [27912-85-2] of similar to the examples 36.2 - 36.4. MS m / e = 282.3 [M + H +]. Example 48 2- (4'-Fluoro-biphenyl-4-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one 48.1 The N- (3-cyano-pyridin-2-yl) - is obtained 2- (4'-fluoro-biphenyl-4-yl) -acetamide from (4 '-fluoro-biphenyl-4-yl) -acetic acid [6908-38-9] in a manner similar to Examples 36.2-36.3 . MS m / e = 348.4 [M + H +]. 48.2 The title compound is obtained from N- (3-cyano-pyridin-2-yl) -2- (4'-fluoro-biphenyl-4-yl) -acetamide in a manner similar to Example 40.2. MS m / e = 348.1 [M + H +]. Example 49 2- (4-m-tolyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one 49.1 The (3-cyano-pyridin-2-yl) -amide of pent-acid is obtained 4-inoic from the pentynoic acid [6089-09-4] in a manner similar to Examples 36.2-36.3. MS m / e = 200.3 [M + H +]. 49.2 Under an argon atmosphere, the bis (triphenylphosphine) palladium (II) chloride ([13965-03-2], 326 mg) and copper (I) iodide (44 mg) are added to a solution of 3-iodotoluene ([ 625-95-6], 506 mg, 2 mmol) and (3-cyano-pyridin-2-yl) -amide of pent-4-inoic acid (508 mg, 3 mmol) in diethylamine (15 ml). The mixture is kept at t.amb. (3 d). The volatiles are evaporated and the residue is taken up in ethyl acetate. After washing (H20) and drying (Na2SO4), the solvent is evaporated and the 5-m-tolyl-pent-4-ynoic acid (3-cyano-pyridin-2-yl) -amide is isolated from the mixture of reaction by column chromatography (silica gel, ethyl acetate / heptane). MS m / e = 290.1 [M + H +]. 49. 3 The 5-m-tolyl-pentanoic acid (3-cyano-pyridin-2-yl) -amide is obtained from the 5-m-tolyl (3-cyano-pyridin-2-yl) -amide of 5-m-tolyl -pent-4-inoic in a manner similar to Example 41.2. MS m / e = 294.4 [M + H +]. 49.4 The title compound is obtained from the (3-cyano-pyridin-2-yl) -amide of 5-m-tolyl-pentanoic acid in a manner similar to Example 40.2. MS m / e = 294.3 [M + H +]. Example 50 2- (1-methyl-4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one 50. 1 Diethyl methylmalonate ([609-08-5], 1175 g, 7 mmol) is added with cooling (0 ° C) to a suspension of NaH (60% in mineral oil, 325 mg, 8 mmol) in ether. of diethyl (30 ml). After 3 h at t.amb. The solvent is evaporated and the residue dissolved in DMF (20 ml). To this solution are added triphenylvinylphosphonium bromide ([5044-52-0], 3.00 g, 8 mmol) and benzaldehyde ([100-52-7], 860 mg, 8 mmol). The reaction mixture is stirred at 100 ° C overnight, taken up in ethyl acetate, washed (H20) and dried (Na2SO4). The solvent is evaporated and diethyl 2-methyl-2- (3-phenyl-allyl) -malonate is isolated from the residue by column chromatography (silica gel, ethyl acetate / heptane). MS m / e = 291.0 [M + H +]. 50. 2 Diethyl 2-diethyl-2- (3-phenyl-propyl) -malonate is obtained from diethyl 2-methyl-2- (3-phenyl-allyl) -malonate in a similar manner to Example 41.2. MS m / e = 293.0 [M + H +]. 50.3 Diethyl 2-methyl-2- (3-phenyl-propyl) -malonate is added to a solution of KOH in ethanol. The mixture is stirred at t.amb. for 5 h and then it is heated to reflux overnight. The solvent is evaporated, the residue is taken up in water and extracted with diethyl ether. The aqueous phase is acidified (HC1) and extracted with ethyl acetate. The organic phase is washed (brine), dried (a2SO4) and the solvent is evaporated. The 2-methyl-5-phenyl-pentanoic acid obtained is sufficiently pure for the next step. MS m / e = 191.4 [M-H ~]. 50.4 2-Methyl-5-phenyl-pentanoic acid (3-cyano-pyridin-2-yl) -amide is obtained from 2-methyl-5-phenyl-pentanoic acid in a similar manner to Examples 36.2-36.3 . MS m / e = 294.3 [M + H +]. 50.5 The title compound is obtained from the (3-cyano-pyridin-2-yl) -amide of 2-methyl-5-phenyl-pentanoic acid in a similar manner to Example 40.2. MS m / e = 294.3 [M + H +].

Example 51 2- (Naphthalen-2-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2-naphthoxyacetic acid [120-23-0] in a similar manner to example 40. MS m / e = 304.0 [M + H +]. Example 52 1-Benzyl-3- (-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -urea The benzyl isocyanate is added to a solution of 2-aminomethyl-3H- pyrido [2,3-d] pyrimidin-4-one (example 24.1) in pyridine; the reaction mixture is maintained at t.amb. during one night. The volatiles are evaporated and the title compound is isolated by reverse phase preparative HPLC from the reaction mixture. MS m / e = 308.4 [M-H ~]. EXAMPLE 53 2- [2- (4-Fluoro-phenyl) -ethoxymethyl] -6-methyl-3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from the 2-amino- 5-methyl-nicotinonitrile [38076-78-7] in a similar manner to example 40. MS m / e = 314.3 [M + H +]. Example 54 2- (4-iodo-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from (4-iodo-phenoxy) -acetic acid [1878-94 -0] similarly to examples 36.2 - 36.4. MS m / e = 380.3 [M + H +].

EXAMPLE 55 2- [3- (4-Fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 3- (4-fluoro-phenoxy) ) -propan-l-ol [104 13-57-2] in a similar way to example 28. MS m / e = 314.1 [MH ~]. Example 56 2- (3-p-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 3-p-tolyloxy-propan-l-ol [ 52449-00-0] similarly to example 28. MS m / e = 310.5 [MH ~]. EXAMPLE 57 2- [3- (2-Fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 3- (2-fluoro-phenoxy) ) -propan-l-ol [145073-40-1] similarly to example 28. MS m / e = 314.3 [MH ~]. Example 58 2- (3-o-tolyloxy-propoxy) -3H-pyrido [2, 3-d] pyrimidin-4 -one The title compound is obtained from 3-o-tolyloxy-propan-l-ol [52448-99-4] in a similar way to example 28. MS m / e = 310.4 [MH ~]. Example 59 2- [2- (2-Fluoro-phenyl) -ethoxymethyl] -7-methyl-3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from the 2-amino- 6-methyl-nicotinonitrile [84647-20-1] and 2- (2-fluoro-phenyl) -ethanol [50919-06-7] in a manner similar to example 36. MS m / e = 312.1 [MH ~]. Example 60 (2-chloro-benzyl) 4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -carbamate. Triethylamine (0.26 ml), 2-chlorobenzyl chloroformate are added. ([39545-31-8], 130 mg) and DMAP (8 mg) to a solution of 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (25.1, 150 mg) in dichloromethane ( 3 mi). The mixture is kept at t.amb. overnight, it is diluted with dichloromethane and washed with water. After drying (a2SO4) and evaporation of the solvent, the title compound of the reaction mixture is isolated by reverse phase preparative HPLC (column Zorbax XdB C18 from Agilent, solvent gradient: CH3CN from 5 to 95% in water with 0.1 % TFA in 7 min, flow rate: 30 ml / min). MS m / e = 343.0 [M-H-]. Example 61 2- [3- (3-Fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that described in Example 28 starting of 3- (3-fluoro-phenoxy) -propan-l-ol [133077-41-5]. MS m / e = 314.1 [M-H-].

EXAMPLE 62 2- (3-m-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that described in example 28 from 3-m -toliloxy-propan-l-ol [13030-21-2]. MS m / e = 310.4 [M-H ~]. EXAMPLE 63 2- [2- (2-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (2-trifluoromethyl-phenyl) ) -ethanol [94022-96-5] in a manner similar to example 36. MS m / e = 348.4 [MH ~]. EXAMPLE 64 2- [2- (2-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (2-methoxy-phenyl) ) -ethanol [7417-18-7] in a similar way to example 36. MS m / e = 310. [MH "] Example 65 2- (2-o-tol.-yl-ethoxymethyl) -3H-pyrido [2 , 3-d] pyrimidin-4 -one The title compound is obtained from 2-o-tolyl-ethanol [19819-98-8] in a similar way to example 36. MS m / e = 296.5 [M + H + EXAMPLE 66 2- [2- (2-Chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (2-chloro) phenyl) -ethanol [19819-95-5] in a manner similar to example 36. E m / e = 314.1 [MH ~] Example 67 2-phenethyloxy-3H-pyrido [2,3-d] pyrimidine-4- The title compound is obtained from 2-phenyl-ethanol [60-12-8] in a manner similar to Example 28. MS m / e = 268.2 [M + H +] Example 68 2- (3, 4- dichloro-benzyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from (3,4-dichloro-phenyl) -methanol [1805-32-9] in a manner similar to Example 28. MS m / e = 322.1 [M + H +]. EXAMPLE 69 2- [2- (4-Fluoro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (4-fluoro-phenyl) ) -ethanol [7589-27-7] in a manner similar to example 28.

MS m / e = 286.1 [M + H +]. EXAMPLE 70 2- (2,4-difluoro-benzyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from (2,4-difluoro-phenyl) -methanol [ 56456-47-4] similar to the example 28. MS m / e = 290.0 [M + H +].

EXAMPLE 71 2- [2- (4-Chloro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 2- (4-chloro-phenyl) ) -ethanol [1875-88-3] in a manner similar to example 28. MS m / e = 302.1 [M + H +]. Example 72 2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 5-phenyl-pentan-1-ol [10521-91-] 2] similarly to example 28. MS m / e = 310.1 [M + H +]. EXAMPLE 73 2- (6-Phenyl-hexyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained from 6-phenyl-hexan-1-ol [10521-91-] 2] similarly to example 28. MS m / e = 324.3 [M + H +]. Example 74 2- [3- (4-Chloro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that described in Example 28 starting of 3- (4-chloro-phenoxy) -propan-l-ol [18673-04-6]. MS m / e = 330.3 [M-H ~]. EXAMPLE 75 2- [3- (2-Chloro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that described in Example 28 starting of 3- (4-chloro-phenoxy) -propan-l-ol [18673-04-6]. MS m / e = 330.3 [M-H ~]. Example 76 2- [2- (3-Chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that described in Example 28 starting of 3- (2-chloro-phenoxy) -propan-l-ol [60222-56-2]. MS m / e = 330.3 [M-H ~]. Example 77 (6-methyl-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester The title compound is obtained in a manner similar to that described in example 28 from 3- (3-chloro-phenoxy) -propan-l-ol [57264-55-8]. MS m / e = 323.5 [M-H ~]. Example 78 6-Chloro-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4 -one 78.1 Ethyl iodoacetate (340 μ? 2.9 mmoles) was added to an ice-cooled solution of 2- (2,5-difluorophenyl) -ethanol (500 mg, 2.4 mmol), silver trifluoromethanesulfonate (685 mg, 2.7 mmol) and 2,6-diol. tert-butylpyridine (820 μ?, 3.6 mmol) in dichloromethane (5 ml). The reaction mixture is stirred at room temperature for 14 h, diluted with dichloromethane and filtered on a Speedex filter. A 1/1 mixture of ice-water / 0.1 N aqueous HC1 is added to the filtrate and the filtrate is extracted twice with dichloromethane. The extracts are combined, washed with an aqueous solution of NaHCO 3 and brine and dried with sodium sulfate. Removal of the solvent under reduced pressure gives a colorless oil, which is purified by column chromatography (silica gel, isopropyl acetate / heptane), obtaining [2- (2, 5-difluoro-phenyl) -ethoxy] -acetate. of ethyl (320 mg, 1.3 mmol; 54%) in the form of a colorless oil. MS m / e = 245.0 [+ H +]. 78.2 In 10 min a 2 M solution of trimethylaluminum in toluene (3.3 ml, 7 mmol) is added to an ice-cooled suspension of dry ammonium chloride (350 mg, 7 mmol) in toluene (4 mL). The mixture is stirred at room temperature for 1 h. A solution of ethyl [2- (2, 5-difluoro-phenyl) -ethoxy] -acetate (320 mg, 1.3 mmol) in toluene (2 mL) is added and the reaction mixture is heated at 80 ° C for 15 minutes. h. It is cooled to 0 ° C, methanol (5 ml) is carefully added and it is stirred at room temperature for 30 min. The solid is filtered and washed with methanol. The filtrate is concentrated to dryness and treated with a 4/1 mixture of iPrOH / acetone (12 ml) for 2 h. The solid was separated by filtration and the filtrate was concentrated to dryness, yielding 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -acetamidine hydrochloride (385 mg, 1.5 mmol, quant. ) in the form of yellow crystals. MS m / e = 215.4 [+ H +]. 78.3 2, 5-Dichloronicotinic acid (50 mg, 260) is added Umoles), TBTU (88 mg, 273 umoles) and DIPEA (130 μ ?, 781 umoles) to a solution of 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -acetamidine hydrochloride (65 mg , 260 μp ??? ße) in DMF (1 ml). The solution is stirred at room temperature for 72 h and poured into a 1/1 ice-water / dichloromethane mixture. The phases are separated, the aqueous phase is extracted twice with dichloromethane, the extracts are combined, washed with brine and dried with sodium sulfate. Removal of the solvent under reduced pressure yields 2, 5-dichloro-N-. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide (97 mg, 250 pmol, 96%) in the form of orange oil, which is used in the next step without further purification. MS m / e = 388.2 [M + H +]. 78.4 The KOtBu (28 mg, 250 μp ??? ee) is added at room temperature to a solution of 2, 5-dichloro-N-. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide (97 mg, 250 μ? -noles) in DMSO (1 ml). The solution is stirred at 50 ° C for 1 h, cooled to room temperature, KOtBu (28 mg, 250 mol) is added and the reaction solution is stirred at 50 ° C for 14 h. The mixture is poured over a 1/1 mixture of isopropyl acetate / ice-water. The phases are separated and the aqueous phase is extracted twice with isopropyl acetate. The extracts are combined, washed three times with brine and dried with sodium sulfate. The solvent is removed under reduced pressure obtaining a yellow solid, which is recrystallized from dichloromethane / heptane, obtaining 6-chloro-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one (8 mg, 23 mmol, 9%) in the form of yellow crystals. MS m / e = 352.3 [M + H +]. Example 79 6-Chloro-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4 -one 79.1 To a solution of 2- (3-chloro-phenyl) ) -ethanol (1.96 g, 12.51 mmol) in THF (55 ml) was added at -78 ° C n-BuLi (8.8 ml, 1.6 M solution in hexane, 13.77 mmol). Then the sodium iodoacetate (2.6 g, 12.51 mmol) is added, the mixture is allowed to warm to room temperature and stirred overnight. The THF is removed and 1N HC1 is added to the remaining residue to adjust the pH to 1. This mixture is extracted twice with dichloromethane, the extracts are combined, dried (Na2SO4) and concentrated. The residual red liquid is dissolved in MeOH (60 ml) and thionyl chloride (1.56 ml, 21.5 mmol) is added dropwise at -15 ° C. The reaction mixture is stirred at room temperature for 1.5 h. Water is added and the mixture is extracted three times with ether. The extracts are combined, washed with brine, dried (Na2SO4) and concentrated. The remaining residue was purified by column chromatography (silica gel, heptane / ethyl acetate from 95: 5 to 88:12) to obtain [2- (3-chloro-phenyl) -ethoxy] -acetic acid methyl ester (2161 g. , 9.45 mmole, 76%) in the form of an orange liquid. MS m / e = 229.2 [M + H +]. 79.2 In a manner similar to the procedure described in Example 78.2, methyl [2- (3-chloro-phenyl) -ethoxy] -acetate is treated with trimethyl-aluminum and ammonium chloride to obtain the hydrochloride of 2- [2- (3-Chloro-phenyl) -ethoxy] -acetamidine in the form of a brown oil. MS m / e = 213.1 [M + H +]. 79.3 Similar to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (3-chloro-phenyl) -ethoxy] -acetamidine in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N- . { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of orange oil. MS m / e = 388.1 [M + H +]. 79.4 Similar to the procedure described in the example 78. 4 is treated with 2, 5-dichloro-N-. { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu to obtain 6-chloro-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of colorless crystals. MS m / e = 350.2 [+ H +]. Example 80 6-Chloro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 80.1 Similar to the procedure described in the example 78. 1 2- (-fluorophenyl) -ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2, β-di-tert-butylpyridine, obtaining [2- (4-fluoro-phenyl) -ethoxy] ] -ethyl acetate in the form of a colorless liquid. NMR-H1 (CDC13) = 1.28 (t, J = 7.2 Hz, 3H), 2.92 (t, J = 7.0 Hz, 2H), 3.73 (t, J = 7.0 Hz, 2H), 4.07 (s, 2H), 4.22 (q, J = 7.2 Hz, 2H), 6.97 (m, 2H), 7.21 (m, 2H). 80.2 Similar to the procedure described in the example 78. 2 [2- (4-Fluoro-phenyl) -ethoxy] -acetic acid ethyl ester is treated with trimethyl-aluminum and ammonium chloride to obtain 2- [2- (4-fluoro-phenyl) -ethoxy] hydrochloride] -acetamidine in the form of a yellow solid. MS m / e = 197.1 [M + H +]. 80.3 Similar to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (4-fluoro-phenyl) -ethoxy] -acetamidine in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N- . { 2- [2- (4-Fluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of orange oil. MS m / e = 370.0 [M + H +]. 80.4 In a manner similar to the procedure described in Example 78.4, 2, 5-dichloro-N- is treated. { 2- [2- (4-Fluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu to obtain 6-chloro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of yellow crystals. MS m / e = 334.4 [M + H +]. Example 81 6-Chloro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 81.1 Similarly to the procedure described in Example 78.1, react the 2- (3-trifluoromethoxy-phenyl) -ethanol with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining [2- (3-trifluoromethoxy-phenyl) -ethoxy] - ethyl acetate in the form of a colorless oil. MS m / e = 293.1 [M + H +]. 81.2 In a manner similar to the procedure described in Example 78.2, ethyl [2- (3-trifluoromethoxy-phenyl) -ethoxy] -acetate is treated with trimethyl-aluminum and ammonium chloride to obtain the hydrochloride of 2- [2- (3-trifluoromethoxy-phenyl) -ethoxy] -acetamidine in the form of an orange oil. MS m / e = 263.1 [M + H +]. 81. 3 Similar to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (3-trifluoromethoxy-phenyl) -ethoxy] -acetamidine in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N- . { l-imino-2- [2- (3-trifluoromethoxy-phenyl) -ethoxy] -ethyl} -nicotinamide in the form of orange oil. E m / e = 436.2 [M + H +]. 81.4 Similar to the procedure described in the example 78. 4 is treated with 2, 5-dichloro-N-. { l-imino-2- [2- (3-trifluoromethoxy-phenyl) -ethoxy] -ethyl} -nicotinamide with KOtBu to obtain 6-chloro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of colorless crystals. MS m / e = 400.1 [M + H +]. Example 82 6-Chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4 -one 82.1 Similarly to the procedure described in example 78. 1 2- (3-chloro-4-fluoro-phenyl) -ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining [2- (3-chloro -4-fluoro-phenyl) -ethoxy] -acetic acid ethyl acetate in the form of a colorless oil. MS m / e = 261.2 [M + H +]. 82. 2 In a manner similar to the procedure described in Example 78.2, [2- (3-chloro-4-fluoro-phenyl) -ethoxy] -acetic acid ethyl ester is treated with trimethyl aluminum and ammonium chloride to obtain the hydrochloride of the compound. - [2- (3-Chloro-4-fluoro-phenyl) -ethoxy] -acetamidine in the form of yellow crystals. E m / e = 231.2 [M + H +]. 82.3 In a manner similar to the procedure described in Example 78.3, 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxy] -acetamidine in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N-. { 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of orange oil. MS m / e = 404.2 [M + H +]. 82.4 Similar to the procedure described in Example 78.4, we deal with the, 5-dichloro-N-. { 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu to obtain 6-chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of crystals orange MS m / e = 368.0 [M + H +]. Example 83 6-Chloro-2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 83.1 In a similar manner to the procedure described in Example 78.1 react 2- (4-chloro-phenyl) -ethanol with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining the '[2- (4-chloro-phenyl) -ethoxy] -ethyl acetate in the form of a colorless liquid. E m / e = 243.2 [M + H +]. 83.2 In a manner similar to the procedure described in Example 78.2, [2- (4-chloro-phenyl) -ethoxy] -acetic acid ethyl ester is treated with trimethyl aluminum and ammonium chloride, yielding the hydrochloride of 2- [2- (4-Chloro-phenyl) -ethoxy] -acetamidine as a white solid. NMR-H1 (DMSO-d6): 2.89 (t, J = 6.9 Hz, 2H), 3.69 (t, J = 6.9 Hz, 2H), 4.29 (s, 2H), 7.273-7.38 (m, 4H), 8.93 (s br, 4H). 83.3 In a manner similar to the procedure described in Example 78.3, 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (4-chloro-phenyl) -ethoxy] -acetamidine in the presence of TBTU and DIPEA, obtaining 2, 5-dichloro-N-. { 2- [2- (4-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of yellow oil. MS m / e = 388.1 [M + H +]. 83.4 In a manner similar to the procedure described in Example 78.4, 2, 5-dichloro-N- is treated. { 2- [2- (4-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu, obtaining 6-chloro-2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of orange crystals. MS m / e = 350.2 [M + H +]. EXAMPLE 84 3- (3-Fluoro-phenyl) -N- (4 -oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide 84.1 To a solution of 2-amino- nicotinamide [13438-65-8] (3.0 g, 21.9 mmol) in CH2C12 (120 ml) and pyridine (10.56 ml, 131.3 mmol) was added at 0 ° C the phthalyl glycyl chloride (5.87 g, 26.3 mmol) . The solution is converted to a white suspension while stirring at 0 ° C for 0.5 hour and at room temperature for 1 hour. The solid was filtered and washed with CH2C12, obtaining 2- [2- (1,3-dioxo-l, 3-dihydro-isoindol-2-yl) -acetylamino] -nicotinamide (7.10 g, 21.9 mmol.; 100%) in the form of a white solid. MS (m / e) = 325.1 [M + H +]. 84.2 A solution of 2- [2- (1,3-dioxo-1,3-dihydro-isoindol-2-yl) -acetylamino] -nicotinamide (7.24 g, 22.3 mmol) is stirred at 100 ° C overnight. and DIPEA (14.4 mL, 111.6 mmol) in DMF (250 mL). The reaction mixture is concentrated, dissolved again in toluene and concentrated to dryness under reduced pressure. The residue was triturated with 100 ml of a 19/1 mixture of EtOAc / MeOH and filtered, yielding 2- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -isoindole-1,3-dione (6.03 g, 19.7 mmol, 88%) as a slightly brown solid. MS (m / e) = 307.2 [M + H +]. 84.3 A suspension of 2- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -isoindole-1,3-dione is stirred at 50 ° C for 3 hours. 1.0 g, 3.26 mmol) and hydrazine monohydrate (0.48 ml, 9.79 mmol) in ethanol (90 ml). The mixture is cooled to room temperature and sodium carbonate (0.38 g, 3.59 mmol) and water (1 mL) are added. The suspension is stirred at room temperature overnight. The solid residue is filtered, triturated with a 4/1 mixture of CH2C12 / MeOH at reflux. A white solid was filtered and triturated with TB E, yielding 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (0.285 g, 1.62 mmol, 50%) as a white solid. MS (m / e) = 176.8 [M + H +]. 84.4 To a suspension of 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (77 mg, 0.39 mmol) in acetonitrile (4 mL) and DMF (0.5 mL) is added successively to DIPEA (0.30 ml, 1.78 mmol), 3- (3-fluorophenyl) propionic acid (60 mg, 0.36 mmol) and BOP-C1 (136 mg, 0.54 mmol). The reaction mixture is stirred at room temperature for 1 hour, concentrated and triturated with CH2C12 / MeOH (4/1). Filtration gives 3- (3-fluoro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide (30 mg, 92 μp. ?? 1? 5; 26%) as a white solid. MS (m / e) = 327.3 [M + H +]. EXAMPLE 85 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one To a solution of 2,5-difluoropyridine-3-acid carboxylic acid (150 mg, 0.94 mmol) in CH2C12 (5 ml) was added dropwise at 0 ° C oxalyl chloride (97 μ ?, 1.13 mmol) and then 2 drops of DMF. The reaction mixture is warmed to room temperature and stirred for 4 h. The reaction mixture is concentrated in vacuo and used for the next step without further purification. The crude acid chloride is dissolved in MeCN (5 ml) and the N, N-diisopropyl-ethyl-amine (345 μ ?, 2.67 mmol) is added thereto and then the hydrochloride salt of the 2- [2- (3 chlorophenyl) -ethoxy] -acetamidine (222 mg, 0.89 mmol) (obtained as described in Example 79.2). The reaction mixture is stirred at room temperature for 16 h and heated to reflux for a further 16 h. The reaction mixture is cooled to room temperature and concentrated in vacuo to obtain a residue, which is partitioned between water and ethyl acetate. The organic phases are combined, washed with HC1 IN HC1, a sat. NaHC03, brine, dried with MgSCa, filtered and concentrated in vacuo, obtaining a crude residue, which is triturated with ether (3x5 ml), obtaining the desired product, 2- [2- (3-chlorophenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one (65 mg, 0.19 mmol, 22%) as a white off-white solid. MS m / e = 334.1 [M + H +]. EXAMPLE 86 2- [2- (3-Chloro-phenyl) -ethoxymethyl] -7-fluoro-3 H -pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that of Example 85 a from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (3-chloro-phenyl) -ethoxy] -acetamidine hydrochloride (Example 79.2). Slightly brown solid. MS m / e = 334.1 [M + H +]. Example 87 2- (5-Methyl-2-phenyl-oxazol-4-yl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide From similar to that described in Example 84.4, from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and (5-methyl-2-phenyl-oxazole- 4-yl) -acetic [107367-98-6] gives 2- (5-methyl-2-phenyl-oxazol-4-yl) -N- (4-oxo-3), 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide as a white solid. MS (m / e) = 376.3 [M + H +]. Example 88 2- [1, 2, 4] Triazol-l-ylmethyl-3H-pyrido [2,3-d] pyrimidin-4 -one 88.1 To a solution of 2-amino-nicotinamide (200 mg, 1.4 mmol) in DMF (3 mi) is added successively to t.amb. 1H-1,2,4-triazole-1-acetic acid [28711-29-7] (185 mg, 1.4 mmol), diisopropylethylamine [7087-68-5] (200 μ ?, 1.4 mmol) and hexafluorophosphate of O- (7-azabenzotriazol-1-yl) -?,?,? ,? ' -tetramethyluronium [200731-31-3] (555 mg, 1.4 mmol). The reaction mixture is stirred for 18 hours. The solvent is removed in vacuo and the residue is digested with dichloromethane, yielding the product as a white, matt solid. Filtration and drying gave 206 mg of 2- (2- [1, 2, 4] triazol-1-yl-acetylamino) -nicotinamide as a matt white solid, which was used without further purification for the next step . 88.2 2- (2- [1, 2, 4] triazol-1-yl-acetylamino) -nicotinamide (206 mg, 0.8 mmol) is dissolved in pyridine (4 mL). The solution is heated in a microwave oven at 150 ° C for 15 min. The solvent was removed in vacuo and the residue was purified by chromatography on silica gel (dichloromethane / methanol gradient) to give 2- [1, 2, 4] triazol-1-ylmethyl-3H-pyrido [2, 3-d] pyrimidin-4-one (18 mg, 72 μG ?????; 9%) in the form of a yellow solid. MS (m / e) = 229.1 [M + H +]. EXAMPLE 89 2- (3-Chloro-phenoxy) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide In a manner similar to that described in Example 84.4 from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and from 3-chlorophenoxyacetic acid [588-32-9] the 2- (3-chloro- phenoxy) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide as a white solid. MS (m / e) = 345.2 [+ H +]. EXAMPLE 90 N- (- ??? - 3,4-Dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -2- (pyridin-2-yloxy) -acetamide In a manner similar to that described in the example 84.4 from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (example 84.3) and (2-pyridinyloxy) -acetic acid. [58530-50-0] yields N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -2- (pyridin-2-yloxy) -acetamide in white solid form. MS (m / e) = 312.0 [M + H +]. EXAMPLE 91 2- [2- (3-Fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 91.1 To a solution of 2- (3-fluoro-phenyl) -ethanol ( 4.0 g, 28.5 mmol) in DMF (60 ml) is added a 60% dispersion of sodium hydride in oil (2.40 g, 60 mmol). The suspension is heated at 60 ° C for 0.75 hours. Chloroacetic acid (4.72 g, 50 mmol) is added dropwise. after 36 hours at 60 ° C the brown reaction mixture is concentrated under reduced pressure to dryness, dissolved in EtOAc and washed with 1M HC1, water and brine. The organic phases are dried with MgSO 4, filtered, the solvent is removed under reduced pressure and the residue is purified by column chromatography (silica gel, EtOAc / heptane, 3/1), obtaining the acid [2- (3- fluorine-phenyl) -ethoxy] -acetic acid (2.02 g, 18 mmol, 36%) as a colorless liquid. MS (m / e) = 197.4 [MH]. "91.2 A solution of [2- (3-fluoro-phenyl) -ethoxy] -acetic acid (1.20 g, 6.05 mmol) is stirred at 0 ° C for 2 hours, EDCI (1.28 g, 6.66 mmol), HOBt (0.90 g, 6.66 mmol) and DIPEA (1.56 mL, 9.08 mmol) in methanol (4 mL). The reaction mixture was concentrated to dryness, dissolved in CH 2 Cl 2 and washed twice. at 1M NaOH and brine, the organic phases are dried with MgSO 4, filtered, the solvent is removed under reduced pressure and the residue is purified by column chromatography (silica gel, EtOAc / heptane, 1/4), obtaining the [2- (3-Fluoro-phenyl) -ethoxy] -acetic acid methyl ester (1.20 g, 5.6 mmol, 93%) as a colorless liquid MS (m / e) = 213.2 [M + H] +. A suspension of 2-amino-nicotinamide (250 mg, 1.82 mmol) and methyl [2- (3-fluorophenyl) -ethoxy] -acetate (464 mg, 2.18 mmol) in THF is treated at room temperature. mi) with LiHMDS (1M solution in THF, 4.6 ml) overnight The yellow suspension is filtered , the filtrate is concentrated to dryness and the residue is purified by column chromatography (silica gel with amino phase, CH2Cl2 / MeOH = 19/1), obtaining 2- [2- (3-fluoro-phenyl) -ethoxymethyl) ] -3H-pyrido [2,3-d] pyrimidin-4-one (303 mg, 1 mmol; 55%) in the form of a white solid. MS (m / e) = 300.2 [M + H] + Example 92 2- [2- (3-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one Similarly As described in Example 91.3, 2-amino-nicotinamide and methyl [2- (3-methoxy-phenyl) -ethoxy] -acetate (obtained from 2- (3-methoxyphenyl) ethanol [5020- 41-7] in a manner similar to Examples 91.1-91.2) in the presence of LiHMDS in THF, obtaining after purification of the crude product with column chromatography (silica gel, EtOAc) 2- [2- (3- methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one as a white solid. MS (m / e) = 312.2 [M + H +]. EXAMPLE 93 7-Fluoro-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one 93.1 The chloride is added dropwise at -15 ° C. thionyl (288 μ ?, 3. 98 mmol) was added to a solution of 5- (4-fluoro-phenyl) -pentanoic acid (520 mg, 2.65 mmol) in methanol (11 mL). The reaction mixture is stirred at room temperature for 1.5 h. Water is added and the mixture is extracted 3 times with diethyl ether. The extracts are combined, washed with water and brine, dried (Na 2 SO 4) and concentrated. The remaining residue was purified by column chromatography (silica gel, ethyl acetate / heptane from 5:95 to 12:88), yielding 5- (4-fluorophenyl) -pentanoate methyl (420 mg, 2 mmol; 75%) in the form of a colorless liquid. MS m / e = 211.0 [M + H +]. 93.2 Similarly to the procedure described in Example 78.2 methyl 5- (4-fluoro-phenyl) -pentanoate is treated with trimethyl-aluminum and ammonium chloride, obtaining the hydrochloride of 5- (4-fluorophenyl) -pentanamidine in the form of a matt white solid. MS m / e = 195.2 [M + H +]. 93.3 The title compound is obtained in a manner similar to Example 85 from 2,6-difluoropyridine-3-carboxylic acid and 5- (4-fluoro-phenyl) -pentanamidine hydrochloride. White solid. MS m / e = 316.1 [M + H +]. Example 94 7-Fluoro-2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 94.1 Similarly to the procedure described in Example 79.1 it becomes 2- (2-Fluorophenyl) -ethanol in methyl [2- (2-fluoro-phenyl) -ethoxy] -acetate. Yellow oil MS m / e = 213.1 [M + H +]. 94. 2 In a manner similar to the procedure described in Example 78.2, [2- (2-fluorophenyl) -ethoxy] -acetic acid methyl ester is treated with trimethyl aluminum and ammonium chloride, obtaining the hydrochloride of 2- [2- (3 -chloro-phenyl) -ethoxy] -acetamidine as a colorless oil. MS m / e = 197.2 [M + H +]. 94.3 The title compound is synthesized in a manner similar to Example 85 using 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (2-fluorophenyl) -ethoxy] -acetamidine, yielding 7-fluoro-2 - [2- (2-Fluorophenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one as the desired product (80%) as a white solid. MS m / e = 318.2 [M + H +]. EXAMPLE 95 N- (β-Fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide 95.1 A suspension is stirred at room temperature for 18 hours of 2-chloro-5-fluoro-nicotinic acid (2.0 g, 11.39 min), HOBt (2.31 g, 17.13 mmol), BOP-C1 (4.37 g, 17.15 mmol), ammonium chloride (1.22 g, 22.86 mmol), DIPEA (12 mL, 66.74 mmol) in DMF (75 mL). The reaction mixture is diluted with EtOAc and washed with water and brine. The organic phases are dried with MgSO 4, filtered and concentrated. The crude product was purified by column chromatography (silica gel, EtOAc), yielding 2-chloro-5-fluoro-nicotinamide (850 mg, 4.9 mmol, 43%) as a white solid. E (m / e) = 175.1 [M + H +]. 95.2 A solution of 2-chloro-5-fluoro-nicotinamide (70 mg, 0.40 mmol) and 4-methoxybenzylamine (550 mg, 4.01 mmol) in ethylene glycol is heated in a microwave oven at 140 ° C for 50 min. my) . A white solid is separated by filtration and the filtrate is concentrated. The residue is dissolved in EtOAc, washed with water and brine, dried with MgSO 4 and the solvent is removed under reduced pressure. The residue was purified by column chromatography (silica gel, EtOAc / heptane = 1/1), yielding 5-fluoro-2- (4-methoxy-benzylamino) -nicotinamide (56 mg, 0.2 mmol, 51%) in white solid form. MS (m / e) = 276.3 [M + H +]. 95.3 5-Fluor-2- (4-methoxy-benzylamino) -nicotinamide (220 mg, 0.80 mmol) in CH2C12 (2 mL) and anisole (1 mL) with TFA (2.57 mL) are treated at 60 ° C for 3 hours. , 34.6 mmoles). The reaction mixture was concentrated to dryness and the residue was purified by column chromatography (silica gel, EtOAc / heptane = 1/4) to obtain 2-amino-5-fluoro-nicotinamide (100 mg, 0.65 mmol; %) in the form of a yellow solid. MS (m / e) = 156.1 [M + H +]. 95. 4 From 2-amino-5-fluoro-nicotinamide, 2-aminomethyl-6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one is synthesized in a similar manner to Example 84.1-84.3. Solid yellow. MS (m / e) = 195.1 [M + H +]. 95.5 A solution of 2-aminomethyl-6-fluoro-3H-pyrido [2] is treated at 0 ° C for 18 hours., 3-d] pyrimidin-4-one (130 mg, 0.67 mmol) in THF (5 mL) with DIPEA (173 mg, 1.34 mmol) and 3-phenyl-propionyl chloride (136 mg, 0.80 mmol). The reaction mixture is diluted with EtOAc, washed with water and brine. The organic phases are dried with MgSO 4, filtered, concentrated and chromatographed (silica gel, EtOAc / heptane = 1/1), obtaining N- (6-fluoro-4-oxo-3,4-dihydro-pyrido). [2, 3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide (6 mg, 13 ymol; 2%) in the form of a yellow solid. MS (m / e) = 327.3 [M + H +]. Example 96 7-Fluoro-2- [2- (3-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 96.1 Similarly to the procedure described in example 78.1 react the 2- (3-trifluoromethyl-phenyl) -ethanol with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining [2- (3-trifluoromethyl-phenyl) -ethoxy] - ethyl acetate in the form of a colorless liquid. MS m / e = 277.2 [M + H +]. 96.2 In a manner similar to the procedure described in Example 78.2, [2- (3-trifluoromethyl-phenyl) -ethoxy] -acetic acid ethyl ester is treated with trimethyl aluminum and ammonium chloride, yielding the hydrochloride of 2- [2- (3-trifluoromethyl-phenyl) -ethoxy] -acetamidine as a brown solid. MS m / e = 247.2 [M + H +]. 96. 3 The title compound is obtained in a manner similar to that of Example 85 from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (3-trifluoromethyl-phenyl) -ethoxy] -acetamidine hydrochloride. Brown solid. MS m / e = 368.1 [M + H +]. Example 97 5-methy1-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one 97.1 5-Methyl-lH-pyrido [2,3-d] pyrimidine is suspended -2,4-dione (H. Junek, I. Wrtilek, Monatsh, Chem. 101, 1130-5, 1970; 2 g, 11 mmol) at room temperature in phosphorus oxychloride (7.7 ml, 85 mmol) and stirred at reflux for 14 h. The reaction mixture is poured onto ice-water, filtered and the filtrate is extracted twice with isopropyl acetate. The extracts are combined, washed with brine, dried with sodium sulfate and the solvent is removed under reduced pressure. The crude product was purified by column chromatography (silica gel, isopropyl acetate / heptane) to obtain 2,4-dichloro-5-methyl-pyrido [2,3-d] pyrimidine (302 mg, 1.4 mmol; 13%) in the form of yellow crystals. E m / e = 214.1 [+ H +]. 97.2 2, 4-Dichloro-5-methyl-pyrido [2,3-d] pyrimidine (302 mg, 1.4 mmol) is suspended at room temperature in a 1N aqueous solution of NaOH (6 mL) and stirred for 1 h . The pH is adjusted to 7 with an aqueous solution of 25% HC1 and the mixture is washed twice with dichloromethane. The aqueous phase was concentrated to dryness under reduced pressure, yielding 344 mg (1.48 mmol, quant. Yield) of 2-chloro-5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one hydrochloride. in the form of matt white solid, which is used in the next step without further purification. MS m / e = 195.9 [M + H +]. 97.3 The hydrochloride of 2-chloro-5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one (36 mg, 155 μg) was dissolved in DMSO (0.8 ml). Molecular sieves of 4A, 5-phenyl-1-pentanol (80 μ ?, 465 and mmol) and potassium tert-butylate (35 mg, 310 mol) are added and the suspension is stirred at 120 ° C for 48 h in an atmosphere of argon. The molecular sieves are separated by filtration, the filtrate is poured onto a mixture 1/1 = water-ice / isopropyl acetate, the phases are separated and the aqueous phase is extracted twice with isopropyl acetate. The extracts are combined, washed with brine, dried with sodium sulfate and the solvent is removed under reduced pressure. The crude product was purified by column chromatography (silica gel, isopropyl acetate / heptane) to obtain 5-methyl-1-2- (5-f in i-1 -pentyloxy) -3H-pyrido [2, 3 -d] pyrimidin-4 -one (16 mg, 50 μg, 32%) in the form of yellow crystals. MS m / e = 324.4 [M + H +]. EXAMPLE 98 6-Chloro-2- (3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one 98.1 In a nitrogen atmosphere and at a temperature of 0 ° C, it is added. slowly a solution of 2,5-dichloropyridine-3-carbonyl chloride [175277-81-3] (4.82 g, 23 mmol) in CHC13 (7 ml) to a solution of methyl aminomethanoimidothioate hydroiodide [4338-95-8] ] (5.00 g, 23 mmol) and triethylamine (6.36 ml, 46 mmol) in pyridine (7 ml). The reaction mixture is stirred at t.amb. during a weekend, it is taken up in ethyl acetate and washed (water). After drying (Na2SO4) and evaporation of the solvent, the residue is purified (column chromatography, silica gel, CH2C12 / MeOH), yielding 1- (2, 5-dichloro-pyridine-3-carbonyl) -2-methyl- isothiourea (3.50 g, 13 mmol, 58%). MS m / e = 262.0 [M + H +]); NMR-H1 (DMSO-d6): d = 2.44 (s, 3H), 8.27 (d, 1H), 8.55 (d, 1H), 9.15 (bs, 1H), 9.55 (bs, 1H). 98.2 Under a nitrogen atmosphere, a solution of 1- (2, 5-dichloro-pyridine-3-carbonyl) -2-methyl-isothiourea (2.44 g, 9 mmol) in DMF (8 ml) is heated for 15 min. ). After cooling, ethanol (8 ml) is added, the hydrochloride of the 6-chloro-2-methylsulfanyl-3H-pyrido [2,3-d] pyrimidin-4-one which has precipitated is filtered off and the solvents are removed residuals with high vacuum overnight (770 mg, 2.9 mmol, 32%). NMR-H1 (DMSO-d6): d = 3.34 (s), 3H), 8.44 (d, 1H), 8.80 (d, 1H), 8.85 (bs, 1H), 8.95 (bs, 1H). 98.3 The hydrochloride of 6-chloro-2-methylsulfanyl-3H-pyrido [2,3-d] pyrimidin-4-one (380 mg, 1.4 mmol) in 2N HC1 (1.4 ml) was heated at reflux for 1 h. The resulting suspension is cooled, diluted with a small amount of water and filtered. The residual solvent is removed from the 6-chloro-lH-pyrido [2,3-d] pyrimidine-2,4-dione hydrochloride obtained by high vacuum over a weekend (230 mg, 0.95 mmol); 68%). NMR-H1 (DMSO-d6): d = 3.37 (bs, 1H), 7.5 (bs, 1H), 7.8 (bs, 1H), 8.25 (d, 1H), 8.30 (d, 1H). 98.4 Under a nitrogen atmosphere, a mixture of 6-chloro-1H-pyrido [2,3-d] pyrimidine-2,4-dione hydrochloride (360 mg, 1.54 mmol) and phosphorus oxychloride (5.6 ml) is refluxed. ). The excess phosphorus oxychloride is evaporated, the black mixture is poured onto ice-water and extracted (CH2C12). The organic phases are combined, dried (Na2SO4) and the solvent is evaporated. The crude 2, 4,6-trichloro-pyrido [2,3-d] pyrimidine is used in the next step without further purification or characterization. 98.5 2, 4,6-trichloro-pyrido [2,3-d] pyrimidine is dissolved (360 mg, crude) in 1N NaOH (6 mL) (in an ultrasonic bath) and stirred at rt. for 30 min. The resulting suspension is extracted with Et20. The aqueous phase is separated, acidified (HC1) and extracted again (EtOAc). The organic phase is dried (Na 2 SO 4), filtered and concentrated to obtain crude 2,6-dichloro-3 H -pyrido [2,3-d] pyrimidin-4-one (MS m / e 214.3 [MH ~] ) that is used without further purification for the next step. 98.6 A solution of 2,6-dichloro-3H-pyrido [2,3-d] pyrimidin-4-one (60 mg, crude), 3-phenoxy is heated in a microwave oven at 180 ° C for 15 min. -l-propanol [6180-61-6] (127 mg, 0.84 mmole) and KOtBu (62 mg, 0.55 mmole) in DIVISO (1 ml). Filter, from the reaction mixture, the title compound (2.3 mg, 6.9 μp, 2.5%, MS m / e = 330.3 [MH "]) is obtained by preparative reverse phase HPLC (Zorbax XdB column). Agilent C18, solvent gradient: CH3CN from 5 to 95% in water with 0.1% TFA in 7 min, flow rate: 30 ml / min.) Example 99 7 -methyl-2- (5-phenyl-pentyloxy) - 3H-pyrido [2,3-d] pyrimidin-4-one 99.1 Similar to the procedure described in the example 97. 2, 2,4-dichloro-7-methyl-pyrido [2,3-d] pyrimidine is treated (R.K. Robins, G.H. Hitchings, J. Am. Chem. Soc. 80, 3449-57, 1958) with a 1N NaOH solution, yielding 2-chloro-7-methyl-3H-pyrido [2,3-d] pyrimidin-4-one hydrochloride as an orange solid. MS m / e = 196.1 [M + H +]. 99.2 Similar to the procedure described in the example 97. 3 the hydrochloride of 2-chloro-7-methyl-3H-pyrido [2,3-d] pyrimidin-4-one is reacted with 5-phenyl-1-pentanol in DMSO in the presence of molecular sieves and tert-butylate potassium, obtaining 7-methyl-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one in the form of yellow crystals. MS m / e = 324.4 [M + H +]. EXAMPLE 100 2- [3- (2-Chloro-phenoxy) -propoxy] -5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one Similarly, the procedure described in Example 97.3 is reacted 2-chloro-5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one hydrochloride with 3- (2-chloro-phenoxy) -propan-l-ol [60222-56-2] in DMSO in the presence of molecular sieves and potassium tert-butylate, obtaining the title compound in the form of matt white crystals. MS m / e = 346.1 [+ H +]. Example 101 7-Fluoro-2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 101.1 Similarly to the procedure described in the example 78. 1 2- (3-fluoro-phenyl) -ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining [2- (3-fluorophenyl) - ethoxy] -ethyl acetate in the form of a colorless liquid. MS m / e = 227.2 [M + H +]. 101.2 Similar to the procedure described in the example 78. 2 [2- (3-Fluoro-phenyl) -ethoxy] -acetic acid ethyl ester is treated with trimethyl aluminum and ammonium chloride, yielding 2- [2- (3-fluoro-phenyl) -ethoxy] hydrochloride] -acetamidine in the form of a yellow solid. MS m / e = 197.1 [M + H +]. 101.3 The title compound is obtained in a manner similar to that of Example 85 from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (3-fluoro-phenyl) -ethoxy] -acetamidine hydrochloride. Slightly brown solid. MS m / e = 318.1 [M + H +]. Example 102 7-Fluoro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that of Example 85 a from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (4-fluoro-phenyl) -ethoxy] -acetamidine hydrochloride (Example 80.2). Slightly brown solid. MS m / e = 318.1 [M + H +]. EXAMPLE 103 3- (2-chloro-phenyl) -N- (4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide In a manner similar to that described in example 84.4, from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (example 84.3) and 3- (2-chlorophenyl) propionic acid [1643-28-3] gives the 3- (2-chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -propionamide as a white solid. MS (m / e) = 342.9 [M + H +]. EXAMPLE 104 3- (3-Chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide In a manner similar to that described in Example 84.4 , starting with 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and 3- (3-chlorophenyl) propionic acid [21640-48-2], the - (3-chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide. The crude product was purified by column chromatography (silica gel with amino phase, CH2Cl2 / MeOH = 4/1) and then triturated with TBME, yielding the title compound as a white solid. MS (m / e) = 342.9 [M + H +]. EXAMPLE 105 2- [2- (2-Chloro-phenyl) -ethoxymethyl] -7-fluoro-3 H -pyrido [2,3-d] pyrimidin-4-one 105.1 Similar to the procedure described in the example 78. 1 2- (2-Chloro-phenyl) -ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2, β-di-tert-butylpyridine, obtaining [2- (2-chloro-phenyl) - ethoxy] -ethyl acetate in the form of a yellow liquid. NMR-H1 (CDC13) = 1.28 (t, J = 7.3 Hz, 3H), 3.09 (t, J = 7.1 Hz, 2H), 3.78 (t, J = 7.1 Hz, 2H), 4.09 (s, 2H), 4.21 (q, J = 7.3 Hz, 2H), 7.13 - 7.23 (m, 2H), 7.29 - 7.37 (m, 2H). 105.2 Similar to the procedure described in the example 78. 2 ethyl [2- (2-chloro-phenyl) -ethoxy] -acetate is treated with trimethyl-aluminum and ammonium chloride, yielding 2- [2- (2-chloro-phenyl) -ethoxy] hydrochloride] -acetamidine in the form of a yellow solid. MS m / e = 213.2 [M + H +]. 105.3 The title compound is obtained in a manner similar to Example 85 from 2,6-difluoropyridine-3-carboxylic acid and from 2- [2- (2-chloro-phenyl) -ethoxy] -acetamidine hydrochloride. Slightly brown solid. MS m / e = 334.2 [M + H +]. EXAMPLE 106 6-Chloro-2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 106.1 Similar to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with the hydrochloride of 2- [2- (2-chloro-phenyl) -ethoxy] -acetamidine (example 105.2) in the presence of TBTU and DIPEA, obtaining the 2-5- dichloro-N-. { 2- [2- (2-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of orange oil. MS m / e = 388.1 [M + H +]. 106.2 Similar to the procedure described in the example 78. 4 is treated with 2, 5-dichloro-N-. { 2- [2- (2-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu, obtaining 6-chloro-2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of matt white crystals. MS m / e = 350.3 [M + H +]. Example 107 6-Fluoro-2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that of Example 85 a from 2,5-difluoropyridine-3-carboxylic acid and 2- [2- (3-fluoro-phenyl) -ethoxy] -acetamidine hydrochloride (example 101). Slightly brown solid. MS m / e = 318.2 [M + H +]. Example 108 6-Chloro-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one 108.1 Similarly to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with the hydrochloride of 5- (4-fluoro-phenyl) -pentanamidine (example 93.2) in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N- [5 - (4-fluoro-phenyl) -1-imino-pentyl] -nicotinamide in the form of a brown oil. MS m / e = 368.1 [M + H +]. 108.2 Similar to the procedure described in the example 78. 4, 2,5-dichloro-N- [5- (4-fluoro-phenyl) -1-imino-pentyl] -nicotinamide was treated with KOtBu, obtaining 6-chloro-2- [4- (4-fluoro- phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of matt white crystals. MS m / e = 332.2 [M + H +]. Example 109 2- [2- (2-Chloro-6-fluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one 109.1 Similarly to the procedure described in example 78. 1 2- (2-chloro-6-fluoro-phenyl) -ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, obtaining [2- (2-chloro -6-fluoro-phenyl) -ethoxy] -acetic acid ethyl acetate in the form of a colorless liquid. NMR-H1 (CDC13) = 1.28 (t, J = 7.1 Hz, 3H), 3.15 (t, J = 7.1 Hz, 2H), 3.73 (t, J = 7.3 Hz, 2H), 4.11 (s, 2H), 4.22 (q, J = 7.1 Hz, 2H), 6.96 (m, 1H), 7.09 - 7.19 (m, 2H). 109.2 Similar to the procedure described in the example 78. 2 ethyl [2- (2-chloro-6-fluoro-phenyl) -ethoxy] -acetate is treated with trimethyl-aluminum and ammonium chloride, obtaining the hydrochloride of 2- [2- (2-chloro-6 -fluor-phenyl) -ethoxy] -acetamidine as a yellow solid. MS m / e = 231.2 [M + H +]. 109.3 The title compound is obtained in a manner similar to Example 85 from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (2-chloro-6-fluoro-phenyl) -ethoxy] hydrochloride] -acetamidine. Matte white solid. MS m / e = 352.2 [M + H +]. Example 110 2- (2-m-tolyl-ethoxymethyl) -3H-pyrido [2, 3-d] pyrimidin-4-one In a manner similar to that described in Example 91.3, 2-amino-nicotinamide and methyl (2-m-tolyl-ethoxy) -acetate (obtained from m-tolyl-ethanol [1875-89-4] in a manner similar to that of Example 91.1-91.2) in the presence of LiH DS in THF, obtained after purification of the crude product by column chromatography (silica gel, EtOAc) and Crystallization from EtOAc / heptane 2- (2-m-tolyl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one as a white solid. MS (m / e) = 296.4 [M + H +]. EXAMPLE 111 2- [2- (4-Chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that of Example 85 a from 2,6-difluoropyridine-3-carboxylic acid and 2- [2- (4-chloro-phenyl) -ethoxy] -acetamidine hydrochloride (example 83.2). Matte white solid. MS m / e = 334.2 [M + H +]. Example 112 3- (4-Chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide In a similar manner to that described in example 104 , starting with 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and 3- (4-chlorophenyl) propionic acid [2019-34-3], the - (4-chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide. The crude product was purified by column chromatography (silica gel with amino phase, CH2Cl2 / MeOH = 4/1) and then triturated with TBME, yielding the title compound as a white solid. MS (m / e) = 342.9 [M + H +]. Example 113 (6-Fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid-benzyl ester 2,5-difluoricotinic acid (547 mg, 3.44 mmol) is added ), TBTU (1.33 g, 4.14 mmol) and DIPEA (3.40 ml, 19.85 mmol) to a solution of benzyl carbamimidoylmethyl carbamate [77390-81-9] (725 mg, 3.51 mmol) in DMF (20 ml). The solution is stirred at room temperature for 5 hours and at 90 ° C for 30 hours. The brown suspension is poured into a 1/1 mixture of an aqueous buffer solution, pH = 5, cooled with ice / dichloromethane. The phases are separated, the aqueous phase is extracted twice with dichloromethane, the extracts are combined, washed with brine and dried with magnesium sulfate. Removal of the solvent under reduced pressure and crystallization (EtOAc / TBME) gives (6-fluoro-4-γ-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamate. of benzyl (250 mg, 0.757 mmol); 22%) in the form of a white solid. MS m / e = 327.1 [M-H ~]. EXAMPLE 114 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to the example 85 from 2,6-difluoropyridine-3-carboxylic acid and from the hydrochloride of 2- [2- (2,5-difluoro-phenyl) -ethoxy] -acetamidine (example 78.2). Matte white solid. MS m / e = 336.3 [M + H +]. Example 115 N- (4-Oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethi) -3-m-tolyl-propionamide In a similar manner to that described in Example 84.4, starting from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and 3- (3-methylphenyl) propionic acid [3751-48-2] yields N- (4- oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-m-tolyl-propionamide as a white solid. MS (m / e) = 323.5 [M + H +]. Example 116 7-Fluoro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to that of Example 85 a from 2,6-difluoropyridine-3-carboxylic acid and from the hydrochloride of 2- [2- (3-trifluoromethoxy-phenyl) -ethoxy] -acetamidine (Example 81.2). Slightly brown solid. MS m / e = 384.1 [M + H +]. EXAMPLE 117 3- (3-Methoxy-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide In a manner similar to that described in example 84.4 , starting from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and 3- (3-methoxyphenyl) propionic acid [10516-71-9], the - (3-methoxy-phenyl) -N- (4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide as a white solid. E (m / e) = 339.1 [M + H +]. EXAMPLE 118 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4 -one The title compound is obtained in a similar manner to Example 85 from 2,6-difluoropyridine-3-carboxylic acid and from the hydrochloride of 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxy] -acetamidine (example 82.2). Matte white solid. MS m / e = 352.2 [M + H +]. EXAMPLE 119 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one The title compound is obtained in a manner similar to the example 85 from 2,5-difluoropyridine-3-carboxylic acid and from the hydrochloride of 2- [2- (2,5-difluoro-phenyl) -ethoxy] -acetamidine (example 78.2). Slightly brown solid. MS m / e = 336.3 [M + H +]. Example 120 (6-Chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester In a similar manner to that described in Example 78.3 and 78.4, starting from 2, 5-dichloronicotinic acid and the benzyl carbamimidoylmethyl carbamate [77390-81-9] yields (6-chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-) ylmethyl) -benzyl carbamate as a white solid. MS (m / e) = 345.3 [M + H +]. Example 121 (7-Chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester In a manner similar to that described in Example 78.3 and 78.4, starting from 2,6-dichloronicotinic acid and benzyl carbamimidoylmethyl carbamate [77390-81-9] yields (7-chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-) ylmethyl) -benzyl carbamate as a light yellow solid. MS (m / e) = 345.3 [M + H +]. Example 122 (7-Fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester In a manner similar to that described in Example 113, from acid 2 , 6-difluoricotinic and benzyl carbamimidoylmethyl carbamate [77390-81-9] yields (7-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -benzyl carbamate (reaction time: 26 hours at room temperature) as a white solid. MS (m / e) = 329.1 [M + H +].

EXAMPLE 123 6-Chloro-2- (2-naphthalen-2-yl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one 123.1 Similar to the procedure described in the example 78. 1 2-naphthalen-2-yl-ethanol is reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridine, yielding (2-naphthalen-2-yl-ethoxy) -acetate of ethyl in the form of a colorless oil. MS m / e = 259.3 [M + H +]. 123.2 Similar to the procedure described in the example 78. 2 ethyl (2-naphthalen-2-yl-ethoxy) -acetate is treated with trimethyl-aluminum and ammonium chloride, yielding 2- (2-naphthalen-2-yl-ethoxy) -acetamidine hydrochloride in the form of solid white matt. MS m / e = 229.3 [M + H +]. 123.3 Similar to the procedure described in the example 78. 3 2,5-dichloronicotinic acid is reacted with 2- (2-naphthalen-2-yl-ethoxy) -acetamidine hydrochloride in the presence of TBTU and DIPEA, obtaining 2,5-dichloro-N- [1 -imino-2- (2-naphthalen-2-yl-ethoxy) -ethyl] -nicotinamide in the form of a yellow oil. MS m / e = 402.3 [M + H +]. 123.4 In a manner similar to the procedure described in Example 78.4, 2,5-dichloro-N- [l-imino-2- (2-naphthalen-2-yl-ethoxy) -ethyl] -nicotinamide is treated with p-phasic carbonate in DMF at 100 ° C for 3 h, yielding 6-chloro-2- (2-naphthalen-2-yl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one as brown crystals. MS m / e = 366.0 [M + H +]. Example 124 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one 124.1 A 1 N aqueous solution of LiOH is added ( 3.3 ml, 3.3 mmol) to a solution of methyl 2-chloro-5-ethyl-nicotinate (325 mg, 1.6 mmol, TY Zhang, EFV Scriven, OR 93/18005 A2) in THF (3.3 ml). The reaction mixture is stirred at room temperature for 3 h, poured into a 1/1 ice-water / isopropyl acetate mixture and acidified with a 1 N aqueous solution of HC1. The phases are separated and the aqueous phase is extracted twice with isopropyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and the solvent was removed under reduced pressure, yielding 2-chloro-5-ethyl-nicotinic acid as a white solid (292 mg, 1.57 mmol, 97%). ), which is used in the next step without further purification. MS m / e = 184.1 [M-H ~]. 124.2 In a manner similar to the procedure described in Example 78.3, 2-chloro-5-ethyl-nicotinic acid is reacted with the hydrochloride of 2- [2- (2, 5-difluorophenyl) -ethoxy] -acetamidine ( example 78.2) in the presence of TBTU and DIPEA, obtaining 2-chloro-N-. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -1-imino-ethyl} -5-ethyl-nicotinamide in the form of a yellow oil. MS m / e = 382.3 [M + H +]. 124.3 In a manner similar to the procedure described in Example 78.4, 2-chloro-N- is treated. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -1-imino-ethyl} -5-ethyl-nicotinamide with potassium carbonate in DMF at 100 ° C for 5 h, yielding 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2, 3 -d] pyrimidin-4 -one in the form of matt white crystals. MS m / e = 346.1 [M + H +]. Example 125 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one 125.1 Similarly to the procedure described in Example 78.3, reacting 2-chloro-5-ethyl-nicotinic acid (example 124.1) with the hydrochloride of 2- [2- (3-chloro-phenyl) -ethoxy] -acetamidine (example 79.2) in the presence of TBTU and DIPEA, obtaining 2-chloro-N-. { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -5-ethyl-nicotinamide in the form of a yellow oil. MS m / e = 380.2 [M + H +]. 125.2 In a manner similar to the procedure described in Example 78.4, 2-chloro-N- is treated. { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -5-ethyl-nicotinamide with potassium carbonate in DMF at 100 ° C for 5 h, yielding 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2, 3-d] ] pyrimidin-4-one in the form of matt white crystals. MS m / e = 344.3 [M + H +]. Example 126 6-Butyl-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one 126.1 Add hexanal (6.06 ml, 50 mmol) and piperidine (0.16 ml) to a solution of methyl cyanoacetate (4.4 ml, 49 mmol) in acetic acid (6.8 ml). The solution is stirred at room temperature for 14 h and poured into a 1/1 ice-water / dichloromethane mixture. The phases are separated and the aqueous phase is extracted twice with dichloromethane. The extracts are combined, washed with ice-water, dried over sodium sulphate and the solvent is removed under reduced pressure, yielding methyl (E) -2-cyano-oct-2-enoate in the form of a yellow oil (9.66 g). , 53 mmoles; rend quant. ), which is used in the next step without further purification. MS m / e = 199.1 [M + NH4 +]. 126.2 Phosphorus oxychloride (4.76 mL, 51 mmol) is added in 10 minutes to an ice-cooled solution of methyl (E) -2-cyano-oct-2-enoate (4.65 g, 26 mmol) in DMF (12 mL). ) in an argon atmosphere. The reaction mixture is stirred at 80 ° C for 14 h and poured onto ice-water. After 3 h the mixture was extracted twice with dichloromethane, the extracts were combined, washed with ice-water and dried over sodium sulfate. Removal of the solvent under reduced pressure gives a brown oil, which is purified by column chromatography (silica gel, isopropyl acetate / hepta.no), yielding methyl 5-butyl-2-chloro-nicotinate (1.01 g, 4.4 mmol, 17%) in the form of a yellow oil. MS m / e = 227.0 [M + H +]. 126.3 In a manner similar to the procedure described in Example 124.1, methyl 5-butyl-2-chloro-nicotinate is treated with LiOH in THF, yielding 5-butyl-2-chloro-nicotinic acid in the form of colorless crystals. MS m / e = 212.2 [M-H ~]. 126.4 In a manner similar to the procedure described in Example 78.3, 5-butyl-2-chloro-nicotinic acid is reacted with 2- [2- (3-chloro-phenyl) -ethoxy] -acetamidine hydrochloride (Example 79.2) ) in the presence of TBTU and DI PEA, obtaining 5-butyl-2-chloro-N-. { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide in the form of yellow oil. MS m / e = 408.3 [M + H +]. 126.5 Similar to the procedure described in Example 78.4, 5-butyl-2-chloro-N- is treated. { 2- [2- (3-Chloro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu in DMSO, obtaining 6-butyl-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of matt white crystals . MS m / e = 370.4 [M-H ~]. Example 127 6-Butyl-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one 127.1 Similar to the procedure described in Example 78.3 the 5-butyl-2-chloro-nicotinic acid (example 126.3) is reacted with the hydrochloride of 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -acetamidine (example 78.2) in the presence of TBTU and DIPEA, obtaining 5-butyl-2-chloro-N-. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -l-imino-ethyl} -nicotinamide in the form of orange oil. MS m / e = 410.1 [M + H +]. 127.2 Similar to the procedure described in Example 78.4, 5-butyl-2-chloro-N- is treated. { 2- [2- (2, 5-difluoro-phenyl) -ethoxy] -1-imino-ethyl} -nicotinamide with KOtBu in DMSO, obtaining 6-butyl-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one in the form of crystals white whites. MS m / e = 374.4 [M + H +]. Example 128 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one 128.1 Similarly to the procedure described in Example 78.3 2-chloro-5-ethyl-nicotinic acid (example 124.1) is reacted with 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxy] -acetamidine hydrochloride (example 82.2) in the presence of TBTU and DIPEA, obtaining 2-chloro-N-. { 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxy] -l-imino-ethyl} -5-ethyl-nicotinamide in the form of a yellow oil. MS m / e = 398.1 [M + H +]. 128.2 In a manner similar to the procedure described in Example 78.4, 2-chloro-N- is treated. { 2- [2- (3-Chloro-4-fluoro-phenyl) -ethoxy] -l-imino-ethyl} -5-ethyl-nicotinamide with KOtBu in DMSO, obtaining 2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4 -one in the form of matt white crystals. MS m / e = 362.1 [M + H +]. EXAMPLE 129 6-Cyclopropyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one 129 Palladium (II) acetate (1 mg) is added under an argon atmosphere. 4. 5 umoles) to a degassed suspension of 6-bromo-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one (20 mg, 55 umoles; example 26), acid cyclopropyl boronic acid (10 mg, 110 umoles), potassium phosphate (59 mg, 275 umoles) and tricyclohexylphosphine (3 mg, 9 umoles) in toluene (360 μ) and water (24 μ). The reaction mixture is heated at 100 ° C for 14 h and poured into a 1/1 isopropyl acetate / ice-cooled brine mixture. The phases are separated, the aqueous phase is extracted twice with isopropyl acetate, the extracts are combined, washed with brine and dried with sodium sulfate. Removal of the solvent under reduced pressure gives a yellow solid which is purified by preparative thin layer chromatography (silica gel, isopropyl acetate / heptane), obtaining 6-cyclopropyl-2- (4-phenyl-butyl) -3H - pyrido [2,3-d] pyrimidin-4-one (1 mg, 3.1 umoles, 6%) in the form of yellow crystals. MS m / e = 320.2 [M + H +]. Example 130 2- (2-Fluoro-phenyl) -ethanesulfonic acid 4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide To an ice-cooled suspension of the 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3, 50 mg, 0.28 mmol) in CH2C12 (2 mL) is added DIPEA (0.10 mL, 0.58 mmol) and chloride of 2- (2-fluoro-phenyl) -ethanesulfonyl (78 mg, 0.35 mmol). The reaction mixture is stirred at 0 ° C for 3 hours. The unreacted 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one is filtered off, the filtrate is concentrated to dryness and the residue is chromatographed (silica gel, EtOAc) to obtain 2- (2-Fluoro-phenyl) -ethanesulfonic acid (4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide (12 mg, 0.034 mmol, 12%) ) in the form of a white solid. MS (m / e) = 363.1 [M + H +]. Example 131 2- (3-Chloro-phenyl) -ethanesulfonic acid-3-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide. Similar to that described in Example 130 , from 2-aminomethyl-3H-pyrido [2,3-d] pyrimidin-4-one (Example 84.3) and from 2- (3-chloro-phenyl) -ethanesulfonyl chloride, the (4-oxo) is obtained. 2- (3-Chloro-phenyl) -ethanesulfonic acid-3-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -amide as a light brown solid. MS (m / e) = 379.1 [M + H +]. Example A Film-coated tablets containing the following ingredients can be manufactured by conventional methods: Ingredients per core tablet: compound of formula (I) 10.0 mg 200.0 mg microcrystalline cellulose 23.5 mg 43.5 mg hydrated lactose 60.0 mg 70.0 mg Povidone K30 12.5 mg 15.0 mg sodium starch glycolate 12.5 mg 17.0 mg magnesium stearate 1.5 mg 4.5 mg ( core weight) 120.0 mg 350.0 mg film layer: hydroxypropyl methyl cellulose 3.5 mg 7.0 mg polyethylene glycol 6000 0.8 mg 1.6 mg talc 1.3 mg 2.6 mg iron oxide (yellow) 0.8 mg 1.6 mg titanium dioxide 0.8 mg 1.6 mg The active ingredient is screened and mixed with microcrystalline cellulose and the mixture is granulated with a solution of polyvinylpyrrolidone in water. The granulate is mixed with sodium starch glycolate and magnesium stearate and compressed, obtaining kernels of 120 and 350 mg, respectively. The cores are coated with an aqueous solution / suspension of the film layer composition just described. EXAMPLE B Capsules containing the following ingredients can be manufactured by conventional methods: Ingredients per capsule compound of formula (I) 25.0 mg lactose 150.0 mg corn starch 20.0 mg talc 5.0 mg The components are sieved, mixed and packed in size 2 capsules. Example C Injectable solutions can have the following composition: compound of the formula (I) 3.0 mg polyethylene glycol 400 150.0 mg acetic acid, sufficient amount up to pH = 5.0 water for injectable solutions, up to 1.0 ml The active ingredient is dissolved in a mixture of polyethylene glycol 400 and water for injections (one part). The pH is adjusted to 5.0 with acetic acid. The volume is adjusted to 1.0 ml by addition of the remaining amount of water. The solution is filtered, it is packaged in vials using an appropriate excess and sterilized. Example D By conventional methods, soft gelatine capsules containing the following ingredients can be manufactured. Content of the capsule compound of the formula 5.0 mg yellow wax 8.0 mg hydrogenated soybean oil 8.0 mg partially hydrogenated vegetable oils 34.0 mg soybean oil 110.0 mg capsule content 165.0 mg gelatin capsule gelatin 75.0 mg glycerin 85% 32.0 mg Karion 83 8.0 mg (dry matter) titanium dioxide 0.4 mg yellow iron oxide 1.1 mg The active ingredient is dissolved in a melt of the other ingredients and the mixture is filled into soft gelatin capsules of the appropriate size. The soft gelatine capsules and their contents are treated according to the usual procedures. EXAMPLE E Small bags containing the following ingredients can be manufactured conventionally: compound of the formula (I) 50.0 mg lactose, fine powder 1015.0 mg microcrystalline cellulose (AVICEL PH 102) 1400.0 mg sodium carboxymethyl cellulose 14.0 mg polyvinylpyrrolidone K 30 10.0 mg magnesium stearate 10.0 mg flavoring additives 1.0 mg The active ingredient is mixed with lactose, microcrystalline cellulose and sodium carboxymethyl cellulose and granulated with a mixture of polyvinylpyrrolidone and water. The granulate is mixed with magnesium stearate and the flavoring additives and packaged in small bags. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Compounds of the formula (I) (i) characterized by X being a single bond, O, N (R3) C (0), N (R3) C (0) 0, OC (0) NR9, N (R9) C (0) NR10 or N ( R9) S02, or, if m is 1, 2 or 3, X can also be C (0) NR9; is a simple link, or, if n is 1, 2, 3, 4, 5 or 6, Y can also be O; R1, R2 and R3 independently of each other are hydrogen, halogen, lower alkyl, fluorine-lower alkyl, lower alkoxy, fluorine-lower alkoxy or cycloalkyl; R4, R5, R6 and R7 independently of each other are hydrogen, fluorine, lower alkyl or fluorine-lower alkyl, or R4 and R5 together with the carbon atom to which they are attached form a ring and -R -R5- is - ( CH2) 2-6"O O R6 and R7 together with the carbon atom to which they are attached form a ring and -R6-R7- is - (CH2) 2_6-, is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine-lower alkoxy, cycloalkyl, fluorine-cycloalkyl, cycloalkyl-oxy, C (0) OH, lower alkoxy- C (0), NH2C (0), N (H, lower alkyl) C (0), N (lower alkyl) 2C (0), OH, lower alkyl-C (0) 0, NH2, N (H, alkyl lower), N (lower alkyl) 2, lower alkyl-C (0) NH, lower alkyl-C (0) N (lower alkyl), NH2S02, N (H, lower alkyl) S02, N (lower alkyl) 2S02, lower alkyl-S02-NH, lower alkyl-S02-N (lower alkyl) or), cyano and phenyl, which is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy and fluorine-lower alkyl; R10 independently of each other are hydrogen, lower alkyl or fluoro-lower alkyl; is 0, 1, 2 or 3; is 0, 1, 2, 3, 4, 5 or 6; where m + n is > 1; and the pharmaceutically acceptable salts and esters thereof. 2. Compounds according to claim 1, characterized in that X is a single bond, 0, N (R9) C (0), N (R9) C (0) 0, 0C (0) NR9 or N (R9) C (0) NR10, or, if m is 1, 2 or 3, X may also be C (0) NR9; And it is a simple link, or, if n is 1, 3, 4, 5 or 6, Y can also be 0; wherein R9 and R10 have the meanings defined in claim 1. 3. Compounds according to any of claims 1-2, characterized in that X is a single bond, 0, N (R9) C (0), N (R9) ) C (0) 0 or N (R9) C (0) NR10 and R9 and R10 have the meanings defined in claim 1. 4. Compounds according to any of claims 1-3, characterized in that X is a single bond , 0, N (R9) C (0) or N (R9) C (0) 0 and R9 have the meaning defined in claim 1. 5. Compounds according to claim 1, characterized in that X is N (R9) S02, wherein R9 has the meaning defined in claim 1. 6. Compounds according to any of claims 1-5, characterized in that Y is a single bond. Compounds according to any of claims 1-5, characterized in that Y is 0. 8. Compounds according to any of claims 1-7, characterized in that R1, R2 and R3 independently of each other are hydrogen, halogen or lower alkyl. 9. Compounds according to any of claims 1 - 8, characterized in that R1 is hydrogen, methyl or fluorine. 10. Compounds according to any of claims 1-9, characterized in that R2 is hydrogen, methyl, ethyl, butyl, fluorine, chlorine or bromine. 11. Compounds according to any of claims 1-10, characterized in that R3 is hydrogen. 12. Compounds according to any of claims 1-11, characterized in that R4, R5, R6 and R7 independently of each other are hydrogen or lower alkyl. 13. Compounds according to any of claims 1 - 12, characterized in that R4, R5, R6 and R7 are hydrogen. 14. Compounds according to any of claims 1 - 13, characterized in that R8 is aryl or heteroaryl, the aryl or heteroaryl is optionally substituted 1 to 3 times by substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, fluorine-lower alkyl, fluorine-lower alkoxy or phenyl, which is optionally substituted by halogen. 15. Compounds according to any of claims 1-14, characterized in that R8 is phenyl or naphthyl, the phenyl is optionally substituted by 1 or 2 substituents independently chosen from the group consisting of halogen and lower alkoxy. 16. Compounds according to any of claims 1-15, characterized in that R8 is phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 2-methoxy-phenyl, 2-chloro-phenyl, 2-fluoro-phenyl, 3,4-dichloro-phenyl, naphthalene-1-yl or naphthalen-2-yl. 17. Compounds according to any one of claims 1-14, characterized in that R8 is 3-chloro-4-fluoro-phenyl, 2,5-difluoro-phenyl or 5-methyl-2-phenyl-oxazol-4-yl. 18. Compounds according to any of claims 1-17, characterized in that m is 0 or 1. 19. Compounds according to any of claims 1-18, characterized in that n is 0, 1, 2, 3 or 4. 20. Compounds according to any of claims 1-19, characterized in that R9 and R10 are hydrogen. 21. Compounds according to any of claims 1-20, characterized in that they are chosen from the group consisting of: 2-benzyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2-phenoxymethyl-3H- pyrido [2,3-d] pyrimidin-4-one, 2- (4-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (5-phenyl-pentyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- (4-ethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4 - ona, 2- (4-fluoro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2-phenethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidin-4 - ona, 2- [2- (3-methoxy-phenyl) -ethyl] -3H-pyrido [2,3-d] pyrimidin -one, 2- [4- (4-chloro-phenyl) -butyl] -3H - pyrido [2,3-d] pyrimidin-4-one, 2- (6-phenyl-hexyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [4- (4-fluorine phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2 -p-Tolyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-chloro-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- ( 2, 3-dimethyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalen-1-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one 2- (-chloro-2-methyl-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin -one, 6-methyl-2- (4-phenyl-butyl) -3H-pyrido [2, 3 -d] pyrimidin-4-one, (4-OXO-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, N- (4-oxo-3, 4- dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -3-phenyl l-propionamide, N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -4-phenyl-butyramide, 6-bromo-2- (phenyl-butyl) - 3H-pyrido [2,3-d] pyrimidin-4-one, 6-bromo-2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [3- (4-methoxy-phenyl) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-phenyl-propoxy) -3H-pyrido [2, 3 -d] pyrimidin-4-one, 2- (4-phenyl-butoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [4- (4-methoxy-phenyl) -butoxy] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (3-pyridin-3-yl-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- ( 2-phenoxy-ethoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (naphthalen-2-yloxy) -ethoxy] -3H-pyrido [2,3-d] pyrimidine 4-one, 2- (3-phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2-phenethyloxymethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-Fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (3,4-difluoro-phenoxy) -propoxy] - 3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (4-methoxy-phen oxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidine- -one, 2- [4- (4-fluoro-phenyl) -3-methyl-butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [5- (4-chloro-phenyl) ) -pentyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (4-fluoro-phenoxy) -propyl] -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-p-tolyl-ethoxymethyl) -3H-pyrido [ 2, 3-d] pyrimidin -one 2- [2- (4-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-benzyloxy-ethyl) ) -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (4'-fluoro-biphenyl-4-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2 - (4-m-tolyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (l-methyl-4-phenyl-butyl) -3H-pyrido [2, 3-d ] pyrimidin-4-one, 2- (naphthalen-2-yloxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 1-benzyl-3- (4-oxo-3, 4-dihydro- pyrido [2,3-d] pyrimidin-2-ylmethyl) -urea, 2- [2- (4-fluoro-phenyl) -et oxymethyl] -6-methyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (4-iodo-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2 - [3- (-fluorophenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-p-tolyloxy-propoxy) -3H-pyrido [2, 3-d ] pyrimidin-4-one 2- [3- (2-fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-o-tolyloxy-propoxy) -3H -pyrant [2,3-d] pyrimidin-4-one
2- [2- (2-Fluoro-phenyl) -ethoxymethyl] -7-methyl-3H-pyrido [2,
3-d] pyrimidin-
4-one, (4-oxo-3,4-dihydro-pyrido [2 , 3-d] pyrimidin-2-ylmethyl) -carbamic acid 2-chloro-benzyl, 2- [3- (3-fluoro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-m-tolyloxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [2 , 3-d] pyrimidin-4-one, 2- [2- (2-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2-o- tolyl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4 -one, 2-phenethyloxy-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3,4-dichloro-benzyl) -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [2- (4-fluoro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (2,4-difluoro-benzyloxy) -3H-pyrido [ 2,3-d] pyrimidin-4-one, 2- [2- (4-chloro-phenyl) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (
5-phenyl) -pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (
6-phenyl-hexyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3 - (4-chloro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (2-chloro-phenoxy) -propoxy] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pir [2,3-d] pyrimidin-4-one and (6-methyl-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester and pharmaceutically acceptable salts and esters thereof. 22. Compounds according to any one of claims 1-21, characterized in that they are chosen from the group consisting of: 2- [4- (4-fluoro-phenyl) -butyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- (2-methoxy-phenoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalene-1-yloxymethyl) -3H-pyrido [2,3- d] pyrimidin-4-one, 6-methyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4-one, (4-oxo-3,4-dihydro-pyrido) [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl- propionamide, 2- [2- (naphthalen-2-yloxy) -ethoxy] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-phenoxy-propoxy) -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- (naphthalen-2-yloxymethyl) ) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-fluoro-phenyl) -ethoxymethyl] -
7-methyl-3H-pyrido [2,3-d] pyrimidine- 4-one, 2- (3, 4-dichloro-benzyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [3- (2-chloro-phenoxy) -propoxy] -3H-pyrido [2,3-d] pyrimidin-4-one and 2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [ 2,3-d] pyrimidin-4-one and the pharmaceutically acceptable salts and esters thereof. 23. Compounds according to any of claims 1-20, characterized in that they are chosen from the group consisting of: 6-chloro-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [ 2,3-d] pyrimidin-4-one, 6-chloro-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6- chloro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 6-chloro-2- [2- (4-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin -one, 3- (3- fluorine-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2, 3-d ] pyrimidin-4-one, 2- (5-methyl-2-phenyl-oxazol-4-yl) -N- (4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -acetamide, 2- [1,2, 4] Triazol-l-ylmethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- (3-chloro -phenoxy) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide, N- (4-oxo-3,4-dihydro-pyrido [2 , 3-d] pyrimidin-2-ylmethyl) -2- (pyridin-2-yloxy) -acetamide, 2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (3-methoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [4- (4- fluorine-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [2- (2-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, N- (6-fluoro-4-oxo-3), 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-phenyl-propionamide, 7-fluoro-2- [2- (3-trifluoromethyl-phenyl) -ethoxymethyl] -3H-pyrido [ 2, 3-d] pyrimidin-4-one, 5-methyl-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- (3 -phenoxy-propoxy) -3H-pyrido [2,3-d] pyrimidin-4-one, 7-methyl-2- (5-phenyl-pentyloxy) -3H-pyrido [2,3-d] pyrimidine-4- ona, 2- [3- (2-chloro-phenoxy) -propoxy] -5-methyl-3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [2- (3- fluorine-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 7-fluoro-2- [2- (4-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2, 3-d] pyrimidin-4-one, 3- (2-chloro-phenyl) -N- (4 -oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 3- (3-chloro-phenyl) -N- (4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, 2- [2- (2-chloro- phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [2- (2-chloro-phenyl) -ethoxymethyl] -3H-pyrido [ 2,3-d] pyrimidin-4 -one, 6-fluoro-2- [2- (3-fluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 6-chloro-2- [4- (4 -fluoro-phenyl) -butyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2-chloro-6-fluoro-phenyl) -ethoxymethyl] -7-fluoro-3H - pyrido [2,3-d] pyrimidin-4-one, 2- (2-m-tolyl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (4 -chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 3- (4-chloro-phenyl) -N- (4-oxo-3, 4- dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -propionamide, (6-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamate of benzyl, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, N- (4-oxo-3, 4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -3-m-toly1-propionamide, 7-fluoro-2- [2- (3-trifluoromethoxy-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 3- (3-methoxy-phenyl) -N- (4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) - propionamide, 2- [2- (3-chloro-4-fluoro-feni l) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -β-fluoro-3H- pyrido [2,3-d] pyrimidin-4-one, (6-chloro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester; -chloro-4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -benzylcarbamate, (7-fluoro-4-oxo-3,4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, 6-chloro-2- (2-naphthalen-2-yl-ethoxymethyl) -3H-pyrido [2,3-d] pyrimidin-4-one, 2 - [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) - ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 6-butyl-2- [2- (3-chloro-phenyl) -ethoxymethyl] -3H-pyrido [2,3 -d] pyrimidin-4-one, 6-butyl-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one, 2- [ 2- (3-Chloro-4-fluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 6-cyclopropyl-2- (4-phenyl-butyl) -3H-pyrido [2,3-d] pyrimidin-4 -one, 2- (2-fluoro-phenyl) -ethanesulfonic acid (4-oxo-3-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide), 2- (3-Chloro-phenyl) -ethanesulfonic acid 4-dihydro-pyrido [2, 3-d] pyrimidin-2-ylmethyl) -amide and the pharmaceutically acceptable salts and esters thereof. 24. Compounds according to any of claims 1-20, characterized in that they are chosen from the group consisting of: 6-chloro-2- [2- (3-chloro-4-fluoro-phenyl) -ethoxymethyl] -3H- pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -6-fluoro-3H-pyrido [2,3-d] pyrimidin-4-one, 2- [2- (3-chloro-phenyl) -ethoxymethyl] -7-fluoro-3H-pyrido [2,3- d] pyrimidin-4-one, 2- (5-methyl-2-phenyl-oxazole-4) -yl) -N- (4-oxo-3, -dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -acetamide, 6-chloro-2- (3-phenoxy-propoxy) -3H-pyrido [2, 3-d] pyrimidin-4-one, (ß-fluoro-4-oxo-3,4-dihydro-pyrido [2,3-d] pyrimidin-2-ylmethyl) -carbamic acid benzyl ester, 2- [ 2- (2,5-difluoro-phenyl) -ethoxymethyl] -β-fluoro-3H-pyrido [2, 3-d] pyrimidin-4-one, 2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -6-ethyl-3H-pyrido [2,3-d] pyrimidin-4-one, 6 -butyl-2- [2- (2, 5-difluoro-phenyl) -ethoxymethyl] -3H-pyrido [2,3-d] pyrimidin-4-one and (4-oxo-3,4-dihydro-pyrido [ 2- (2-Fluoro-phenyl) -ethanesulfonic acid 2, 3-d] pyrimidin-2-ylmethyl) -amide and the pharmaceutically acceptable salts and esters thereof. Process for the preparation of compounds of the formula (I) according to any of claims 1-24, characterized in that it consists in converting a compound of the formula (II) by intramolecular condensation in the compound of the formula (I), wherein 1, R2, R3, R4, R5, R6, R7, R8, m, n, X and Y have according to any of the claims 1-24 26. Compounds according to any of claims 1-24, characterized in that they are obtained by a process according to claim 25. 27. Pharmaceutical compositions, characterized in that they contain a compound according to any of claims 1-24 and a pharmaceutically acceptable carrier and / or adjuvant. 28. Compounds according to any of claims 1-24, characterized in that they are for use as therapeutically active substances. 29. Compounds according to any of claims 1-24, characterized in that they are for use as therapeutically active substances intended for the treatment and / or prevention of diseases that are modulated with HM74A agonists. 30. Method for the treatment and / or prevention of diseases that are modulated with HM74A agonists, in particular for the treatment and / or prevention of high levels of lipids, high cholesterol levels, atherosclerotic diseases, dyslipidemia, HDL cholesterol low, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, disturbed or improbable cognitive function, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver, characterized in that it consists of administering a compound according to any of claims 1 - 24 a a human being or an animal. 31. Use of the compounds according to any of claims 1-24 for the treatment and / or prevention of diseases that are modulated with HM74A agonists. 32. Use of the compounds according to any of claims 1-24 for the treatment and / or prevention of high lipid levels, high cholesterol levels, atherosclerotic diseases, dyslipidemia, low HDL cholesterol, hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, cognitive function upset or unlikely, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / fibrosis of the liver. 33. Use of the compounds according to any of claims 1-24 for the manufacture of medicaments for the treatment and / or prevention of diseases that are modulated with HM74A agonists. 34. Use of the compounds according to any of claims 1-24 for the manufacture of medicaments for the treatment and / or prevention of high lipid levels, high cholesterol levels, atherosclerotic diseases, dyslipidemia, low HDL cholesterol , hypertriglyceridemia, thrombosis, angina pectoris, peripheral vascular disease, stroke, diabetes, diabetes mellitus not dependent on insulin, metabolic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, function cognitive disorder or unlikely, sepsis, inflammatory diseases, asthma, arthritis, colitis, pancreatitis and cholestasis / liver fibrosis.